Field-calibrated model of melt, refreezing, and runoff for polar ice caps : Application to Devon Ice Cap

Acknowledgments R.M.M. was supported by the Scottish Alliance for Geoscience, Environment and Society (SAGES). The field data collection contributed to the validation of the European Space Agency Cryosat mission and was supported by the Natural Sciences and Engineering Research Council, Canada, the Meteorological Service of Canada (CRYSYS program), the Polar Continental Shelf Project (an agency of Natural Resources Canada), and by UK Natural Environment Research Council consortium grant NER/O/S/2003/00620. Support for D.O.B. was provided by the Canadian Circumpolar Institute and the Climate Change Geoscience Program, Earth Sciences Sector, Natural Resources Canada (ESS contribution 20130371). Thanks are also due to the Nunavut Research Institute and the communities of Resolute Bay and Grise Fjord for permission to conduct fieldwork on Devon Ice Cap. M.J. Sharp, A. Gardner, F. Cawkwell, R. Bingham, S. Williamson, L. Colgan, J. Davis, B. Danielson, J. Sekerka, L. Gray, and J. Zheng are thanked for logistical support and field assistance during the data collection. We thank Ruzica Dadic, two other anonymous reviewers, and the Editor, Bryn Hubbard, for their helpful comments on an earlier version of this paper and which resulted in significant improvements.Peer reviewedPublisher PD

Site-Selective Excitation And Polarized Absorption Spectra Of Nd3+ In Sr-5(Po4)(3)F And Ca-5(Po4)(3)F

Polarized absorption and fluorescence spectra were analyzed to establish individual energy (Stark) levels of Nd3+ ions in host crystals of Sr-5(PO4)(3)F (SFAP) and Ca-5(PO4)(3)F (FAP). Site-selective excitation and fluorescence facilitated differentiation between Nd3+ ions in emitting sites-associated with 1.06 mu m stimulated emission, and nonemitting Nd3+ ions in other sites. Measurements were made on samples containing different concentrations of Nd3+ at 4 K and higher temperatures. Substitution of Nd3+ for Sr2+ or Ca2+ was accompanied by passive charge compensation during crystal growth. Crystal-field splitting calculations were performed according to site for Stark levels of Nd3+ ions identified spectroscopically. We obtained a final set of crystal-field parameters B-nm for Nd3+ ions in fluorescing sites with a rms, deviation of 7 cm(-1) (52 levels in Nd:SFAP) and 8 cm(-1) (59 levels in Nd:FAP). For one of the nonemitting sites in Nd:FAP we obtained a final set of B-nm parameters which gave a rms deviation of 6 cm(-1) between 46 experimental and calculated levels

Modification by hemochromatosis gene polymorphisms of the association between traffic-related air pollution and cognition in older men: a cohort study

Background: Previous studies found effect modification of associations between traffic-related air pollution and cardiovascular outcomes by polymorphisms in the hemochromatosis gene (HFE). As traffic-related air pollution may impact cognition through effects on cardiovascular health or through mechanisms which may also influence cardiovascular outcomes, we hypothesized that HFE polymorphisms would also modify a previously observed association between traffic-related air pollution exposure and cognition in older men. Methods: We considered data from 628 participants of the VA Normative Aging Study. We estimated long term exposure to black carbon (BC), a marker of traffic related air pollution, using a spatio-temporal land use regression model. We assessed cognition using the Mini-Mental State Examination (MMSE), a test of global function, and performance on a battery of other tests, covering a wide range of domains. We investigated whether variants of HFE C282Y and H63D modified the association between BC and having a low MMSE score using logistic models with generalized estimating equations and multiplicative interaction terms. Similarly, we assessed whether HFE variants modified the association between BC and performance on the cognitive battery using linear mixed models with multiplicative interaction terms. Results: Our results suggest modification of the BC-cognition association by HFE C282Y, although the test of interaction did not achieve statistical significance. In multivariable-adjusted models, participants who lacked a HFE C282Y variant (CC) exhibited an adverse association between BC and total cognition z-score (beta for a doubling in BC concentration: -0.061, 95% CI: -0.115, -0.007), while we did not observe an association in participants with at least one variant genotype (CY or YY) (beta for a doubling in BC concentration: 0.073, 95% CI: -0.081, 0.228; p-value for interaction: 0.11). The pattern of association was similar for analyses considering performance on the Mini-Mental State Examination. There was little evidence to support effect modification of the BC-cognition association by the HFE H63D genotype. Conclusions: Our data suggest that older adults who lack an HFE C282Y variant may be more susceptible to an adverse effect of traffic-related air pollution exposure on cognition. This finding and the proposed biological mechanism require confirmation

Addressing data integration challenges to link ecological processes across scales

Data integration is a statistical modeling approach that incorporates multiple data sources within a unified analytical framework. Macrosystems ecology – the study of ecological phenomena at broad scales, including interactions across scales – increasingly employs data integration techniques to expand the spatiotemporal scope of research and inferences, increase the precision of parameter estimates, and account for multiple sources of uncertainty in estimates of multiscale processes. We highlight four common analytical challenges to data integration in macrosystems ecology research: data scale mismatches, unbalanced data, sampling biases, and model development and assessment. We explain each problem, discuss current approaches to address the issue, and describe potential areas of research to overcome these hurdles. Use of data integration techniques has increased rapidly in recent years, and given the inferential value of such approaches, we expect continued development and wider application across ecological disciplines, especially in macrosystems ecology

Management and outcomes of gastrointestinal congenital anomalies in low, middle and high income countries: Protocol for a multicentre, international, prospective cohort study

Introduction: Congenital anomalies are the fifth leading cause of death in children globally, contributing an estimated half a million deaths per year. Very limited literature exists from low and middle income countries (LMICs) where most of these deaths occur. The Global PaedSurg Research Collaboration aims to undertake the first multicentre, international, prospective cohort study of a selection of common congenital anomalies comparing management and outcomes between low, middle and high income countries (HICs) globally.Methods and Analysis: The Global PaedSurg Research Collaboration consists of surgeons, paediatricians, anaesthetists and allied healthcare professionals involved in the surgical care of children globally. Collaborators will prospectively collect observational data on consecutive patients presenting for the first time, with one of seven common congenital anomalies (oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation and Hirschsprung\u27s disease).Patient recruitment will be for a minimum of 1 month from October 2018 to April 2019 with a 30-day post-primary intervention follow-up period. Anonymous data will be collected on patient demographics, clinical status, interventions and outcomes using REDCap. Collaborators will complete a survey regarding the resources and facilities for neonatal and paediatric surgery at their centre.The primary outcome is all-cause in-hospital mortality. Secondary outcomes include the occurrence of post-operative complications. Chi-squared analysis will be used to compare mortality between LMICs and HICs. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors.Ethics and Dissemination: At the host centre, this study is classified as an audit not requiring ethical approval. All participating collaborators have gained local approval in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for open access publication in a peer reviewed journal.Trial Registration Number: NCT03666767

Making Maps Of The Cosmic Microwave Background: The MAXIMA Example

This work describes Cosmic Microwave Background (CMB) data analysis algorithms and their implementations, developed to produce a pixelized map of the sky and a corresponding pixel-pixel noise correlation matrix from time ordered data for a CMB mapping experiment. We discuss in turn algorithms for estimating noise properties from the time ordered data, techniques for manipulating the time ordered data, and a number of variants of the maximum likelihood map-making procedure. We pay particular attention to issues pertinent to real CMB data, and present ways of incorporating them within the framework of maximum likelihood map-making. Making a map of the sky is shown to be not only an intermediate step rendering an image of the sky, but also an important diagnostic stage, when tests for and/or removal of systematic effects can efficiently be performed. The case under study is the MAXIMA data set. However, the methods discussed are expected to be applicable to the analysis of other current and forthcoming CMB experiments.Comment: Replaced to match the published version, only minor change

The promoter from SlREO, a highly-expressed, root-specific Solanum lycopersicum gene, directs expression to cortex of mature roots

Root-specific promoters are valuable tools for targeting transgene expression, but many of those already described have limitations to their general applicability. We present the expression characteristics of SlREO, a novel gene isolated from tomato (Solanum lycopersicum L.). This gene was highly expressed in roots but had a very low level of expression in aerial plant organs. A 2.4-kb region representing the SlREO promoter sequence was cloned upstream of the uidA GUS reporter gene and shown to direct expression in the root cortex. In mature, glasshouse-grown plants this strict root specificity was maintained. Furthermore, promoter activity was unaffected by dehydration or wounding stress but was somewhat suppressed by exposure to NaCl, salicylic acid and jasmonic acid. The predicted protein sequence of SlREO contains a domain found in enzymes of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. The novel SlREO promoter has properties ideal for applications requiring strong and specific gene expression in the bulk of tomato root tissue growing in soil, and is also likely to be useful in other Solanaceous crop

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

<p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt

Site-selective excitation and polarized absorption and emission spectra of trivalent thulium and erbium in strontium fluorapatite

Polarized fluorescence spectra produced by site-selective excitation, and conventional polarized absorption spectra were obtained for Tm3+ and Er3+ ions individually incorporated into single crystals of strontium fluorapatite, Sr-5(PO4)(3)F, also known as SFAP. Substitution of the trivalent rare earth ion for divalent strontium was achieved by passive charge compensation during Czochralski growth of the fluorapatite crystals. Spectra were obtained between 1780 and 345 nm at temperatures from 4 K to room temperature on crystals having the hexagonal structure [P6(3)/m(C-6h(2))]. The polarized fluorescence spectra due to transitions from multiplet manifolds of Tm3+(4f(12)), including D-1(2), (1)G(4), and H-3(4) to manifolds H-3(6) (the ground-state manifold), F-3(4), H-3(5), H-3(4), and F-3(3) were analyzed for the details of the crystal-field splitting of the manifolds. Fluorescence Lifetimes were measured for Tm3+ transitions from D-1(2), (1)G(4), and H-3(4) at room temperature and from (1)G(4) at 16 K. Results of the analysis indicate that the majority of Tm3+ ions occupy sites having C-s symmetry. A point-charge lattice-sum calculation was made in which the crystal-field components, A(nm), were determined assuming that trivalent thulium replaces divalent strontium in the metal site having C-s symmetry. Results support the conclusion that the nearest-neighbor fluoride (F-) is replaced by divalent oxygen (O2-), thus preserving overall charge neutrality and local symmetry. Crystal-field splitting calculations predict energy levels in agreement with results obtained from an analysis of the experimental data. By varying the crystal-field parameters, B-nm, we obtained a rms difference of 7 cm(-1) between 43 calculated and experimental Stark levels for Tm3+(4f(12)) in Tm:SFAP. Absorption and fluorescence spectra are also reported for Er3+ ions in Er:SFAP. Measurement of the temporal decay of the room temperature fluorescence from the I-4(11/2) and I-4(13/2) manifolds yielded fluorescence lifetimes of 230+/-20 mu s and 8.9+/-0.1 ms, respectively. The experimental Stark levels obtained from an analysis of the spectroscopic data were compared with a crystal-field splitting calculation. The initial set of B-nm parameters for Er3+(4f(11)) was established from the three-parameter theory and the final set of B-nm parameters obtained for Tm3+(4f(12)) in Tm:SFAP. The best overall agreement between calculated and experimental Stark levels is 8 cm(-1) for 48 Stark levels, representing 12 observed multiplet manifolds of Er3+(4f(11)) in Er:SFAP