Hepatic resection and transplantation for peripheral cholangiocarcinoma

Background: Recent publications have questioned the role of orthotopic liver transplantation (OLT) in treating advanced or unresectable peripheral cholangiocarcinoma (Ch-Ca). Study Design: We reviewed our experience with Ch- Ca to determine survival rates, recurrence patterns, and risk factors in 54 patients who underwent either hepatic resection or OLT between 1981 and 1994. Liver transplantation was performed in patients with unresectable tumors (n = 12) and in those with advanced cirrhosis (n = 8). There were 33 women (61%) and 21 men (39%), with a mean age of 54.3 years. The median followup period was 6.8 years. Prognostic risk factors were analyzed by univariate and multivariate analyses. Results: Mortality within 30 days was 7.4%. Overall patient and tumor-free survival rates were 64% and 57% at 1 year, 34% and 34% at 3 years, and 26% and 27% at 5 years after operation. Thirty-two patients (59.3%) experienced tumor recurrence. Univariate analysis revealed that multiple tumors, bilobar tumor distribution, regional lymph node involvement, presence of metastasis, positive surgical margins, and advanced pTNM stages were significant negative predictors of both tumor-free and patient survival. Multivariate analysis revealed that positive margins, multiple tumors, and lymph node involvement were independently associated with poor prognosis. When patients with these three negative predictors were excluded, the patient survivals at 1, 3, and 5 years were 74%, 64%, and 62%, respectively. Conclusions: Both hepatic resection and OLT are effective therapies for Ch- Ca when the tumor can be removed with adequate margins, the lesion is singular, and lymph nodes are not involved

Intentionality versus Constructive Empiricism

By focussing on the intentional character of observation in science, we argue that Constructive Empiricism – B.C. van Fraassen’s much debated and explored view of science – is inconsistent. We then argue there are at least two ways out of our Inconsistency Argument, one of which is more easily to square with Constructive Empiricism than the other

Manifestly Supersymmetric RG Flows

Renormalisation group (RG) equations in two-dimensional N=1 supersymmetric field theories with boundary are studied. It is explained how a manifestly N=1 supersymmetric scheme can be chosen, and within this scheme the RG equations are determined to next-to-leading order. We also use these results to revisit the question of how brane obstructions and lines of marginal stability appear from a world-sheet perspective.Comment: 22 pages; references added, minor change

The ducky^{2J} Mutation in Cacna2d2 Results in Reduced Spontaneous Purkinje Cell Activity and Altered Gene Expression

The mouse mutant ducky and its allele ducky^{2J} represent a model for absence epilepsy characterized by spike-wave seizures and cerebellar ataxia. These mice have mutations in Cacna2d2, which encodes the α₂δ-2 calcium channel subunit. Of relevance to the ataxic phenotype, α₂δ-2 mRNA is strongly expressed in cerebellar Purkinje cells (PCs). The Cacna2d2du2J mutation results in a 2 bp deletion in the coding region and a complete loss of α₂δ-2 protein. Here we show that du^{2J}/du^{2J} mice have a 30% reduction in somatic calcium current and a marked fall in the spontaneous PC firing rate at 22°C, accompanied by a decrease in firing regularity, which is not affected by blocking synaptic input to PCs. At 34°C, du^{2J}/du^{2J} PCs show no spontaneous intrinsic activity. DU^{2J}/du^{2J} mice also have alterations in the cerebellar expression of several genes related to PC function. At postnatal day 21, there is an elevation of tyrosine hydroxylase mRNA and a reduction in tenascin-C gene expression. Although du^{2J}/+ mice have a marked reduction in α₂δ-2 protein, they show no fall in PC somatic calcium currents or increase in cerebellar tryrosine hydroxylase gene expression. However, du^{2J}/+ PCs do exhibit a significant reduction in firing rate, correlating with the reduction in α₂δ-2. A hypothesis for future study is that effects on gene expression occur as a result of a reduction in somatic calcium currents, whereas effects on PC firing occur as a long-term result of loss of α₂δ-2 and/or a reduction in calcium currents and calcium-dependent processes in regions other than the soma

EIT and diffusion of atomic coherence

We study experimentally the effect of diffusion of Rb atoms on Electromagnetically Induced Transparency (EIT) in a buffer gas vapor cell. In particular, we find that diffusion of atomic coherence in-and-out of the laser beam plays a crucial role in determining the EIT resonance lineshape and the stored light lifetime.Comment: 5 pages, 8 figure

One-point functions in massive integrable QFT with boundaries

We consider the expectation value of a local operator on a strip with non-trivial boundaries in 1+1 dimensional massive integrable QFT. Using finite volume regularisation in the crossed channel and extending the boundary state formalism to the finite volume case we give a series expansion for the one-point function in terms of the exact form factors of the theory. The truncated series is compared with the numerical results of the truncated conformal space approach in the scaling Lee-Yang model. We discuss the relevance of our results to quantum quench problems.Comment: 43 pages, 20 figures, v2: typos correcte

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

Lessons from crossing symmetry at large N

20 pages, v2: Assumptions stated more clearly, version published in JHEPWe consider the four-point correlator of the stress tensor multiplet in N=4 SYM. We construct all solutions consistent with crossing symmetry in the limit of large central charge c ~ N^2 and large g^2 N. While we find an infinite tower of solutions, we argue most of them are suppressed by an extra scale \Delta_{gap} and are consistent with the upper bounds for the scaling dimension of unprotected operators observed in the numerical superconformal bootstrap at large central charge. These solutions organize as a double expansion in 1/c and 1/\Delta_{gap}. Our solutions are valid to leading order in 1/c and to all orders in 1/\Delta_{gap} and reproduce, in particular, instanton corrections previously found. Furthermore, we find a connection between such upper bounds and positivity constraints arising from causality in flat space. Finally, we show that certain relations derived from causality constraints for scattering in AdS follow from crossing symmetry.Peer reviewe

Large field of view, fast and low dose multimodal phase-contrast imaging at high x-ray energy

X-ray phase contrast imaging (XPCI) is an innovative imaging technique which extends the contrast capabilities of ‘conventional’ absorption based x-ray systems. However, so far all XPCI implementations have suffered from one or more of the following limitations: low x-ray energies, small field of view (FOV) and long acquisition times. Those limitations relegated XPCI to a ‘research-only’ technique with an uncertain future in terms of large scale, high impact applications. We recently succeeded in designing, realizing and testing an XPCI system, which achieves significant steps toward simultaneously overcoming these limitations. Our system combines, for the first time, large FOV, high energy and fast scanning. Importantly, it is capable of providing high image quality at low x-ray doses, compatible with or even below those currently used in medical imaging. This extends the use of XPCI to areas which were unpractical or even inaccessible to previous XPCI solutions. We expect this will enable a long overdue translation into application fields such as security screening, industrial inspections and large FOV medical radiography – all with the inherent advantages of the XPCI multimodality

Interpretation and the Constraints on International Courts

This paper argues that methodologies of interpretation do not do what they promise – they do not constrain interpretation by providing neutral steps that one can follow in finding out a meaning of a text – but nevertheless do their constraining work by being part of what can be described as the legal practice