Interlending and document supply: Hopes and fears for 1992

1992 will bring the Single European Market in which many of the existing barriers to European integration will be removed. This applies not only to trade but free movement of goods, rights of residence and work and many other aspects of life. This should be an opportunity to improve the free flow of documenta between countries through the interlibrary loan and document supply network . Customs barriers and restrictions on agency agreements for publishers may make life easier but there is no immediate sign on monetary union which would simplify the payment for international interlending transactions. However, many of the barriers that exist will not be removed by the changes in 1992. Problema will still exist with telecommunications and postal services with differing prices and, worse, different standards of service. The difficult issue of copyright will not be resolved as the EC is not at present looking at reprography as an area of harmonization. Other barriers such as language and professional reluctance to cooperate internationally cannot be changed by legislation. Although 1992 may bring some improvements, there will still be a long way to go.Con la creación en 1992 del Mercado Unico Europeo y la desaparición de muchas barreras ahora existentes, de mercado, de derecho de residencia y trabajo, etc. se abre la oportunidad de mejorar la circulación libre de documentos entre los países a través del préstamo interbibliotecario y las redes de suministro de documentos, pero todavía no hay signos inmediatos de unión monetaria que simplificaría el pago del intercambio internacional, y no parecen de solución inmediata los problemas de telecomunicación y servicios postales con diferentes precios y diferentes normas de servicio, así como los derivados de los derechos de autor. Otras barreras tales como los diferente, idiomas y el rechazo de los profesionales a cooperar internacionalmente no cambiarían con la legislación comunitaria. Aunque 1992 traerá algunas mejoras, todavía hay un largo camino para recorrer

Restrictive covenants in Xanadu

Legal scholarship is naturally inclined towards explanations and justifications of contemporary law. In the case of restrictive covenants and building schemes this has led to a distorted perception of the historical record, as revealed in recorded case reports dating from the nineteenth century. It is argued that the restrictive covenant had its historical genesis not in a response to industrialisation and mass urbanisation, but in the developments of resort towns in the eighteenth and early nineteenth centuries, as a response to the needs of land developers. Furthermore, it is argued that a better historical understanding of these origins illuminates contemporary problems concerned with the adaptability of law and the potential roles of law in development

Inference on inspiral signals using LISA MLDC data

In this paper we describe a Bayesian inference framework for analysis of data obtained by LISA. We set up a model for binary inspiral signals as defined for the Mock LISA Data Challenge 1.2 (MLDC), and implemented a Markov chain Monte Carlo (MCMC) algorithm to facilitate exploration and integration of the posterior distribution over the 9-dimensional parameter space. Here we present intermediate results showing how, using this method, information about the 9 parameters can be extracted from the data.Comment: Accepted for publication in Classical and Quantum Gravity, GWDAW-11 special issu

Psychosis risk candidate ZNF804A localizes to synapses and regulates neurite formation and dendritic spine structure

BackgroundVariation in the gene encoding zinc finger binding protein 804A (ZNF804A) is associated with schizophrenia (SCZ) and bipolar disorder (BP). Evidence suggests that ZNF804A is a regulator of gene transcription and is present in nuclear and extranuclear compartments. However, a detailed examination of ZNF804A distribution and its neuronal functions has yet to be performed.MethodsThe localization of ZNF804A protein was examined in neurons derived from human neural progenitor cells (hNPCs), human induced pluripotent stem cells (hiPSCs) or in primary rat cortical neurons. Additionally, siRNA-mediated knockdown of ZNF804A was conducted to determine its role in neurite formation, maintenance of dendritic spine morphology and responses to activity-dependent stimulations.ResultsEndogenous ZNF804A protein localized to somato-dendritic compartments and co-localized with the putative synaptic markers in young neurons derived from hNPCs and hiPSCs. In mature rat neurons, Zfp804A, the homolog of ZNF804A, was present in a subset of dendritic spines and co-localized with synaptic proteins in specific nanodomains, as determined by superresolution microscopy. Interestingly, knockdown of ZNF804A attenuated neurite outgrowth in young neurons, an effect potentially mediated by reduced neuroligin-4 (NLGN4) expression. Furthermore, knockdown of ZNF804A in mature neurons resulted in the loss of dendritic spine density, and impaired responses to activity-dependent stimulation.ConclusionsThese data reveal a novel subcellular distribution for ZNF804A within somato-dendritic compartments and a nanoscopic organisation at excitatory synapses. Moreover, our results suggest that ZNF804A plays an active role in neurite formation, maintenance of dendritic spines and activity-dependent structural plasticity

Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer : a Mendelian randomisation analysis

BACKGROUND: Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). METHODS: We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. RESULTS: No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96-1.03, P value = 0.90) with CRC was shown. CONCLUSIONS: Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.Peer reviewe

Modifiable pathways for colorectal cancer : a mendelian randomisation analysis

Background Epidemiological studies have linked lifestyle, cardiometabolic, reproductive, developmental, and inflammatory factors to the risk of colorectal cancer. However, which specific factors affect risk and the strength of these effects are unknown. We aimed to examine the relationship between potentially modifiable risk factors and colorectal cancer. Methods We used a random-effects model to examine the relationship between 39 potentially modifiable risk factors and colorectal cancer in 26 397 patients with colorectal cancer and 41 481 controls (ie, people without colorectal cancer). These population data came from a genome-wide association study of people of European ancestry, which was amended to exclude UK BioBank data. In the model, we used genetic variants as instruments via two-sample mendelian randomisation to limit bias from confounding and reverse causation. We calculated odds ratios per genetically predicted SD unit increase in each putative risk factor (OR SD) for colorectal cancer risk. We did mendelian randomisation Egger regressions to identify evidence of potential violations of mendelian randomisation assumptions. A Bonferroni-corrected threshold of p=1.3 x 10(-3) was considered significant, and p values less than 0.05 were considered to be suggestive of an association. Findings No putative risk factors were significantly associated with colorectal cancer risk after correction for multiple testing. However, suggestive associations with increased risk were noted for genetically predicted body fat percentage (OR SD 1.14 [95% CI 1.03-1.25]; p=0.0086), body-mass index (1.09 [1.01-1.17]; p=0.023), waist circumference (1.13 [1.02-1.26]; p=0.018), basal metabolic rate (1.10 [1.03-1.18]; p=0.0079), and concentrations of LDL cholesterol (1.14 [1.04-1.25]; p=0.0056), total cholesterol (1.09 [1.01-1.18]; p=0.025), circulating serum iron (1.17 [1.00-1.36]; p=0.049), and serum vitamin B12 (1.21 [1.04-1.42]; p=0.016), although potential pleiotropy among genetic variants used as instruments for vitamin B12 constrains the finding. A suggestive association was also noted between adult height and increased risk of colorectal cancer (OR SD 1.04 [95% CI 1.00-1.08]; p=0.032). Low blood selenium concentration had a suggestive association with decreased risk of colorectal cancer (OR SD 0.85 [95% CI 0.75-0.96]; p=0.0078) based on a single variant, as did plasma concentrations of interleukin-6 receptor subunit a (also based on a single variant; 0.98 [0.96-1.00]; p=0.035). Risk of colorectal cancer was not associated with any sex hormone or reproductive factor, serum calcium, or circulating 25-hydroxyvitamin D concentrations. Interpretation This analysis identified several modifiable targets for primary prevention of colorectal cancer, including lifestyle, obesity, and cardiometabolic factors, that should inform public health policy. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Q-ball dynamics from atomic Bose-Einstein condensates

Relativistic scalar field theories with a conserved global charge Q possess often (meta)stable spherically symmetric soliton solutions, called Q-balls. We elaborate on the perfect formal analogy which exists between Q-balls, and spherically symmetric solitons in certain non-relativistic atomic Bose-Einstein condensates, for which the dominant interatomic interaction can be tuned attractive. In a harmonic trap, present in existing experiments, the Q-ball solution is modified in an essential way. If the trap is significantly prolongated in one direction, however, then genuine solitons do appear, and actual experimental data can be obtained for some of the Q-ball properties studied numerically in the relativistic cosmological context, such as their formation and collisions. We also suggest conditions under which the same cosmologically relevant analogies could be extended to the fully three-dimensional case.Comment: 16 pages. v2: clarifications and references adde