MendelianRandomization v0.5.0: updates to an R package for performing Mendelian randomization analyses using summarized data.

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added to the package or updated in recent years. These features can be divided into four categories: robust methods for Mendelian randomization, methods for multivariable Mendelian randomization, functions for data visualization, and the ability to load data into the package seamlessly from the PhenoScanner web-resource. We provide examples of the graphical output produced by the data visualization commands, as well as syntax for obtaining suitable data and performing a Mendelian randomization analysis in a single line of code

Warped Spectroscopy: Localization of Frozen Bulk Modes

We study the 10D equation of motion of dilaton-axion fluctuations in type IIB string compactifications with three-form flux, taking warping into account. Using simplified models with physics comparable to actual compactifications, we argue that the lightest mode localizes in long warped throats and takes a mass of order the warped string scale. Also, Gukov-Vafa-Witten superpotential is valid for the lightest mass mode; however, the mass is similar to the Kaluza-Klein scale, so the dilaton-axion should be integrated out of the effective theory in this long throat regime (leaving a constant superpotential). On the other hand, there is a large hierarchy between flux-induced and KK mass scales for moderate or weak warping. This hierarchy agrees with arguments given for trivial warping. Along the way, we also estimate the effect of the other 10D supergravity equations of motion on the dilaton-axion fluctuation, since these equations act as constraints. We argue that they give negligible corrections to the simplest approximation.Comment: 24pp + appendices, 6 figs, JHEP3 class; v2. corrected reference; v3. added clarifications; v4. corrected typo

Paediatric glaucoma in Scotland

Background The primary aim was to estimate the incidence of primary and secondary childhood glaucoma in Scotland over a 2-year period. The secondary aim was to gauge the confidence and experience of ophthalmologists in Scotland in managing these patients. Methods A 7 question electronic survey was distributed to all consultant members of the Scottish Paediatric Club and Scottish Glaucoma Club. Respondents were asked to report the number of cases and types of childhood glaucoma they had managed in the last 2 years. Respondents were also asked about experience and confidence in a range of glaucoma procedures, number of patients requiring referral to specialist centres and interest in the development of a centre of excellence in Scotland. Results The survey returned a 56% response rate, reporting 85 new cases of paediatric glaucoma in Scotland over the preceding 2 years. 11 (12.9%) had primary glaucoma and 74 (87.1%) had secondary glaucoma. The most common subtype of secondary glaucoma was uveitic glaucoma (n = 29). None of the respondents declared confidence or experience in trabeculotomy or goniotomy procedures. Eleven children required referral to a specialist unit outside Scotland. 85.7% of respondents felt Scotland would benefit from a specialist unit for paediatric glaucoma. Conclusions This survey reflects an appetite for a specialist service for paediatric glaucoma in Scotland. However, further consideration is needed to determine if there is sufficient patient load to maintain such a service.Publisher PDFPeer reviewe

Liver Parasites and Body Condition in Relation to Environmental Contaminants in Caribou (Rangifer tarandus) from Labrador, Canada

Over the last several decades, elders and hunters of the Innu Nation in Labrador, Canada, have expressed concerns over perceived declines in environmental health and the integrity of country food, including caribou. The primary objective of this study was to determine links between specific health parameters and contaminants found in caribou from the George River herd. Twenty-seven caribou killed by local Innu hunters between February and December 2001 were evaluated for gross and microscopic pathology, body condition, liver parasitology, and contaminant levels in kidney and fat. Overall, the sampled caribou appeared to be in adequate body condition for the time of year, and no clinically significant lesions were found. Concentrations of selenium, metals (Hg, Cd, and Pb), 20 organochlorine pesticides (HCB, a-HCH, g-HCH, aldrin, dieldrin, methoxychlor, mirex, a- and b-endosulfan, heptachlor, heptachlor epoxide, g-CHL, cis-CHL, trans-nonachlor, and o,p'- and p,p'-DDD, DDE, DDT), and 24 PCB congeners were within the ranges reported for caribou in Canada. In general, contaminant levels were relatively low, with the exception of cadmium in kidneys (geometric mean: 6.5 μg/g wet weight; range: 1.5–44.0 μg/g). Two types of liver parasites were found: the liver fluke Fascioloides magna (prevalence: 78%; geometric mean abundance: 4.2 flukes/caribou) and a tapeworm larva consistent with Taenia hydatigena (prevalence: 50%; geometric mean abundance: 0.6 larvae/caribou). Using multiple variable regression analysis, we found renal concentrations of cadmium to be positively associated, and selenium to be negatively associated, with F. magna abundance.Ces dernières décennies, les aînés et les chasseurs de la nation montagnaise du Labrador, au Canada, ont exprimé des inquiétudes au sujet du déclin de la santé de l’environnement et de l’intégrité de la nourriture provenant de la campagne, telle que le caribou. L’objectif principal de cette étude consistait à déterminer les liens qui existent entre certains paramètres de santé précis et les contaminants se trouvant dans le caribou du troupeau de la rivière George. Vingt-sept caribous ayant été tués par les chasseurs montagnais de la région entre les mois de février et de décembre 2001 ont subi des examens pathologiques macroscopiques et microscopiques, en plus d’avoir été évalués pour en déterminer l’état du corps, la parasitologie du foie et les taux de contaminants dans le foie et le gras. Dans l’ensemble, l’état des corps de caribous échantillonnés semblait adéquat pour cette période de l’année et aucune lésion clinique importante n’a été signalée. Les concentrations de sélénium, de métaux (Hg, Cd et Pb), de 20 pesticides organochlorés (HCB, a-HCH, g-HCH, aldrine, dieldrine, méthoxychlore, mirex, a- et b-endosulfane, heptachlore, heptachlorépoxyde, g-CHL, cis-CHL, trans-nonachlore ainsi que o,p'- et p,p'-DDD, DDE, DDT) et de 24 congénères de PCB s’établissaient dans les étendues signalées pour le caribou au Canada. En général, les niveaux de contaminants étaient relativement faibles, à l’exception du cadmium se trouvant dans les reins (moyenne géometrique : 6,5 μg/g poids humide; étendue : 1,5–44,0 mg/g). Deux types de parasites du foie ont été trouvés : la douve Fascioloides magna (prévalence : 78 %; abondance moyenne géométrique : 4,2 douves/caribou) et un cestode du genre Taenia hydatigena (prévalence : 50 %; abondance moyenne géométrique : 0,6 larves/caribou). Nous avons également réalisé une analyse de régression à variables multiples qui nous a permis de constater que les concentrations de cadmium sont positivement associées et celles de sélénium sont négativement associées à l’abondance de F. magna

Exploring a string-like landscape

We explore inflationary trajectories within randomly-generated two-dimensional potentials, considered as a toy model of the string landscape. Both the background and perturbation equations are solved numerically, the latter using the two-field formalism of Peterson and Tegmark which fully incorporates the effect of isocurvature perturbations. Sufficient inflation is a rare event, occurring for only roughly one in $10^5$ potentials. For models generating sufficient inflation, we find that the majority of runs satisfy current constraints from WMAP. The scalar spectral index is less than 1 in all runs. The tensor-to-scalar ratio is below the current limit, while typically large enough to be detected by next-generation CMB experiments and perhaps also by Planck. In many cases the inflationary consistency equation is broken by the effect of isocurvature modes.Comment: 24 pages with 8 figures incorporated, matches version accepted by JCA

The Universal Kaehler Modulus in Warped Compactifications

We construct the effective theory of the universal Kaehler modulus in warped compactifications using the Hamiltonian formulation of general relativity. The spacetime dependent 10d solution is constructed at the linear level for both the volume modulus and its axionic partner, and nontrivial cancellations of warping effects are found in the dimensional reduction. Our main result is that the Kaehler potential is not corrected by warping, up to an overall shift in the background value of the volume modulus. We extend the analysis beyond the linearized approximation by computing the fully backreacted 10d metric corresponding to a finite volume modulus fluctuation. Also, we discuss the behavior of the modulus in strongly warped regions and show that there are no mixings with light Kaluza-Klein modes. These results are important for the phenomenology and cosmology of flux compactifications.Comment: 28 pages, 1 figure; v2. corrected typos, added refs & minor clarification

Phase II Study of Paclitaxel in Patients With Soft Tissue Sarcomas

Purpose. Patients with soft tissue sarcoma (STS) who have previously received standard chemotherapy including adriamycin (doxorubicin), ifosfamide, cyclophosphamide and DTIC (dacarbazine) have very limited therapeutic options. It is important to identify new drugs with some activity in this disease and we therefore undertook this trial to determine the antitumor activity of paclitaxel (Taxol)

Integrated modelling for economic valuation of the role of forests and woodlands in drinking water provision to two African cities

Rapidly growing economies often have high population growth, resulting in agricultural expansion in rural areas and increased water demand in urban areas. Conversion of forests and woodlands to agriculture may threaten safe and reliable water supply in cities. This study assesses the regulating functions and economic values of forests and woodlands in meeting the water needs of two major cities in Tanzania and proposes an integrated modelling approach with a scenario-based analysis to estimate costs of water supply avoided by forest conservation. We use the process-based hydrological Soil and Water Assessment Tool (SWAT) to simulate the role of woody habitats in the regulation of hydrological flow and sediment control. We find that the forests and woodlands play a significant role in regulating sediment load in rivers and reducing peak flows, with implications for the water supply from the Ruvu River to Dar es Salaam and Morogoro. A cost-based value assessment under water treatment works conditions up to 2016 suggests that water supply failure due to deforestation would cost Dar es Salaam USD 4.6-17.6 million per year and Morogoro USD 308 thousand per year. Stronger enforcement of forest and woodland protection in Tanzania must balance water policy objectives and food security

Modular Design of Self-Assembling Peptide-Based Nanotubes.

An ability to design peptide-based nanotubes (PNTs) rationally with defined and mutable internal channels would advance understanding of peptide self-assembly, and present new biomaterials for nanotechnology and medicine. PNTs have been made from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we show that blunt-ended α-helical barrels, that is, preassembled bundles of α-helices with central channels, can be used as building blocks for PNTs. This approach is general and systematic, and uses a set of de novo helical bundles as standards. One of these bundles, a hexameric α-helical barrel, assembles into highly ordered PNTs, for which we have determined a structure by combining cryo-transmission electron microscopy, X-ray fiber diffraction, and model building. The structure reveals that the overall symmetry of the peptide module plays a critical role in ripening and ordering of the supramolecular assembly. PNTs based on pentameric, hexameric, and heptameric α-helical barrels sequester hydrophobic dye within their lumens.N.C.B. thanks the EPSRC-funded Bristol Centre for Functional Nanomaterials Centre for Doctoral Training for a postgraduate scholarship (EP/G036780/1). F.T. and D.N.W. thank the Leverhulme Trust for funding (RPG-2012-536). D.N.W. holds a Royal Society Wolfson Research Merit Award.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b0397

The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15

Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formatio