The logic of the future in quantum theory

According to quantum mechanics, statements about the future made by sentient beings like us are, in general, neither true nor false; they must satisfy a many-valued logic. I propose that the truth value of such a statement should be identified with the probability that the event it describes will occur. After reviewing the history of related ideas in logic, I argue that it gives an understanding of probability which is particularly satisfactory for use in quantum mechanics. I construct a lattice of future-tense propositions, with truth values in the interval $[0,1]$, and derive logical properties of these truth values given by the usual quantum-mechanical formula for the probability of a history

The first legal mortgagor: a consumer without adequate protection?

This article contends that the UK government’s attempt to create a well-functioning consumer credit market will be undermined if it fails to reform the private law framework relating to the first legal mortgage. Such agreements are governed by two distinct regulatory regimes that are founded upon very different conceptions of the mortgagor. The first, the regulation of financial services overseen by the Financial Conduct Authority, derives from public law and is founded upon a conception of the mortgagor as “consumer”. The other is land law, private law regulation implemented by the judiciary and underpinned by a conception of the mortgagor as “landowner”. Evidence suggests that the operation of these two regimes prevents mortgagors from receiving fair and consistent treatment. The current reform of financial services regulation therefore will change only one part of this governance regime and will leave mortgagors heavily reliant upon a regulator that still has to prove itself. What this article argues is that reform of the rules of private law must also be undertaken with the aim of initiating a paradigm shift in the conception of the mortgagor from “landowner” to “consumer”. Cultural shifts of this kind take time but the hope is that this conceptual transformation will occur in time to deter the predicted rise in mortgage possessions

Spontaneous bilateral distal ulna fracture: an unusual complication in a rheumatoid patient

Bilateral ulna stress fractures are extremely rare. Patients with rheumatoid arthritis have osteopenic bone secondary to a variety of causes. We report a case of bilateral stress fractures of the ulna in an elderly patient with rheumatoid arthritis, and literature on this condition is reviewed. Prompt recognition and activity modification are essential to treat this rare injury. Recovery can take up to 12 weeks

A panel of genes methylated with high frequency in colorectal cancer

Background: The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests. Methods: Combined epigenomic methods - activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment - were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP). Results: Combined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in \u3e50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas. Conclusions: This study has characterised a panel of 23 genes that show elevated DNA methylation in \u3e50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers

SNPs Occur in Regions with Less Genomic Sequence Conservation

Rates of SNPs (single nucleotide polymorphisms) and cross-species genomic sequence conservation reflect intra- and inter-species variation, respectively. Here, I report SNP rates and genomic sequence conservation adjacent to mRNA processing regions and show that, as expected, more SNPs occur in less conserved regions and that functional regions have fewer SNPs. Results are confirmed using both mouse and human data. Regions include protein start codons, 3′ splice sites, 5′ splice sites, protein stop codons, predicted miRNA binding sites, and polyadenylation sites. Throughout, SNP rates are lower and conservation is higher at regulatory sites. Within coding regions, SNP rates are highest and conservation is lowest at codon position three and the fewest SNPs are found at codon position two, reflecting codon degeneracy for amino acid encoding. Exon splice sites show high conservation and very low SNP rates, reflecting both splicing signals and protein coding. Relaxed constraint on the codon third position is dramatically seen when separating exonic SNP rates based on intron phase. At polyadenylation sites, a peak of conservation and low SNP rate occurs from 30 to 17 nt preceding the site. This region is highly enriched for the sequence AAUAAA, reflecting the location of the conserved polyA signal. miRNA 3′ UTR target sites are predicted incorporating interspecies genomic sequence conservation; SNP rates are low in these sites, again showing fewer SNPs in conserved regions. Together, these results confirm that SNPs, reflecting recent genetic variation, occur more frequently in regions with less evolutionarily conservation

Prion protein interaction with soil humic substances: environmental implications

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders caused by prions. Animal TSE include scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids. Effective management of scrapie in many parts of the world, and of CWD in North American deer population is complicated by the persistence of prions in the environment. After shedding from diseased animals, prions persist in soil, withstanding biotic and abiotic degradation. As soil is a complex, multi-component system of both mineral and organic components, it is important to understand which soil compounds may interact with prions and thus contribute to disease transmission. Several studies have investigated the role of different soil minerals in prion adsorption and infectivity; we focused our attention on the interaction of soil organic components, the humic substances (HS), with recombinant prion protein (recPrP) material. We evaluated the kinetics of recPrP adsorption, providing a structural and biochemical characterization of chemical adducts using different experimental approaches. Here we show that HS act as potent anti-prion agents in prion infected neuronal cells and in the amyloid seeding assays: HS adsorb both recPrP and prions, thus sequestering them from the prion replication process. We interpreted our findings as highly relevant from an environmental point of view, as the adsorption of prions in HS may affect their availability and consequently hinder the environmental transmission of prion diseases in ruminants

A hydraulically driven colonoscope

BACKGROUND: Conventional colonoscopy requires a high degree of operator skill and is often painful for the patient. We present a preliminary feasibility study of an alternative approach where a self-propelled colonoscope is hydraulically driven through the colon. METHODS: A hydraulic colonoscope which could be controlled manually or automatically was developed and assessed in a test bed modelled on the anatomy of the human colon. A conventional colonoscope was used by an experienced colonoscopist in the same test bed for comparison. Pressures and forces on the colon were measured during the test. RESULTS: The hydraulic colonoscope was able to successfully advance through the test bed in a comparable time to the conventional colonoscope. The hydraulic colonoscope reduces measured loads on artificial mesenteries, but increases intraluminal pressure compared to the colonoscope. Both manual and automatically controlled modes were able to successfully advance the hydraulic colonoscope through the colon. However, the automatic controller mode required lower pressures than manual control, but took longer to reach the caecum. CONCLUSIONS: The hydraulic colonoscope appears to be a viable device for further development as forces and pressures observed during use are comparable to those used in current clinical practice

A Common Carcinogen Benzo[a]pyrene Causes Neuronal Death in Mouse via Microglial Activation

BACKGROUND: Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels. CONCLUSIONS/SIGNIFICANCE: Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our study throws light on other health hazards that such pollutants may exert

Effective Long-Distance Pollen Dispersal in Centaurea jacea

BACKGROUND: Agri-environment schemes play an increasingly important role for the conservation of rare plants in intensively managed agricultural landscapes. However, little is known about their effects on gene flow via pollen dispersal between populations of these species. METHODOLOGY/PRINCIPAL FINDINGS: In a 2-year experiment, we observed effective pollen dispersal from source populations of Centaurea jacea in restored meadows, the most widespread Swiss agri-environment scheme, to potted plants in adjacent intensively managed meadows without other individuals of this species. Potted plants were put in replicated source populations at 25, 50, 100 m and where possible 200 m distance from these source populations. Pollen transfer among isolated plants was prevented by temporary bagging, such that only one isolated plant was accessible for flower visitors at any one time. Because C. jacea is self-incompatible, seed set in single-plant isolates indicated insect mediated effective pollen dispersal from the source population. Seed set was higher in source populations (35.7+/-4.4) than in isolates (4.8+/-1.0). Seed set declined from 18.9% of that in source populations at a distance of 25 m to 7.4% at 200 m. At a distance of 200 m seed set was still significantly higher in selfed plants, indicating long-distance effective pollen dispersal up to 200 m. Analyses of covariance suggested that bees contributed more than flies to this long-distance pollen dispersal. We found evidence that pollen dispersal to single-plant isolates was positively affected by the diversity and flower abundance of neighboring plant species in the intensively managed meadow. Furthermore, the decline of the dispersal was less steep when the source population of C. jacea was large. CONCLUSIONS: We conclude that insect pollinators can effectively transfer pollen from source populations of C. jacea over at least 200 m, even when "recipient populations" consisted of single-plant isolates, suggesting that gene flow by pollen over this distance is very likely. Source population size and flowering environment surrounding recipient plants appear to be important factors affecting pollen dispersal in C. jacea. It is conceivable that most insect-pollinated plants in a network of restored sites within intensively managed grassland can form metapopulations, if distances between sites are of similar magnitude as tested here