Enhanced Survival and Neuronal Differentiation of Adrenal Chromaffin Cells Cografted into the Striatum with NGF-producing Fibroblasts

Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. Improved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, however, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdifferentiation may occur in vivo has not been determined. We assessed the effects of cografting chromaffin cells with primary fibroblasts genetically engineered to express NGF. Chromaffin cells from 10 d old rats were implanted with NGF-producing or beta- galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopamine treated adult rats of the same strain. Eight weeks postgrafting, chromaffin cells cografted with NGF- producing fibroblasts displayed many of the features of mature sympathetic neurons such as large somata, long processes, transmitter vesicles similar to those found in neurons, and positive immunolabeling for the neuronal markers neurofilament, MAP2 and SCG10. Chromaffin- derived neuron number was also significantly enhanced in the presence of NGF-producing fibroblasts. While control fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did not induce neuronal transdifferentiation. These results demonstrate that chromaffin cells cografted with NGF-producing fibroblasts undergo transdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified

Simplifying Algebra in Feynman Graphs, Part III: Massive Vectors

A T-dualized selfdual inspired formulation of massive vector fields coupled to arbitrary matter is generated; subsequently its perturbative series modeling a spontaneously broken gauge theory is analyzed. The new Feynman rules and external line factors are chirally minimized in the sense that only one type of spin index occurs in the rules. Several processes are examined in detail and the cross-sections formulated in this approach. A double line formulation of the Lorentz algebra for Feynman diagrams is produced in this formalism, similar to color ordering, which follows from a spin ordering of the Feynman rules. The new double line formalism leads to further minimization of gauge invariant scattering in perturbation theory. The dualized electroweak model is also generated.Comment: 39 pages, LaTeX, 8 figure

The first recorded outbreak of cryptosporidiosis due to Cryptosporidium cuniculus (formerly rabbit genotype), following a water quality incident

Background: We report the first identified outbreak of cryptosporidiosis with Cryptosporidium cuniculus following a water quality incident in Northamptonshire, UK. Methods: A standardised, enhanced Cryptosporidium exposure questionnaire was administered to all cases of cryptosporidiosis after the incident. Stool samples, water testing, microscopy slides and rabbit gut contents positive for Cryptosporidium were typed at the Cryptosporidium Reference Unit, Singleton Hospital, Swansea. Results: Twenty-three people were microbiologically linked to the incident although other evidence suggests an excess of 422 cases of cryptosporidiosis above baseline. Most were adult females; unusually for cryptosporidiosis there were no affected children identified under the age of 5 years. Water consumption was possibly higher than in national drinking water consumption patterns. Diarrhoea duration was negatively correlated to distance from the water treatment works where the contamination occurred. Oocyst counts were highest in water storage facilities. Conclusions: This outbreak is the first caused by C. cuniculus infection to have been noted and it has conclusively demonstrated that this species can be a human pathogen. Although symptomatically similar to cryptosporidiosis from C. parvum or C. hominis, this outbreak has revealed some differences, in particular no children under 5 were identified and females were over-represented. These dissimilarities are unexplained although we postulate possible explanations

Global conformal anomaly in N=2 string

We show the existence of a global anomaly in the one-loop graphs of N=2 string theory, defined by sewing tree amplitudes, unless spacetime supersymmetry is imposed. The anomaly is responsible for the non-vanishing maximally helicity violating amplitudes. The supersymmetric completion of the N=2 string spectrum is formulated by extending the previous cohomological analysis with an external spin factor; the target space-time spin-statistics of these individual fields in a selfdual background are compatible with previous cohomological analysis as fields of arbitrary spin may be bosonized into one another. We further analyze duality relations between the open and closed string amplitudes and demonstrate this in the supersymmetric extension of the target space-time theory through the insertion of zero-momentum operators.Comment: 29 pages, LaTeX, one figur

The superstring Hagedorn temperature in a pp-wave background

The thermodynamics of type IIB superstring theory in the maximally supersymmetric plane wave background is studied. We compute the thermodynamic partition function for non-interacting strings exactly and the result differs slightly from previous computations. We clarify some of the issues related to the Hagedorn temperature in the limits of small and large constant RR 5-form. We study the thermodynamic behavior of strings in the case of $AdS_3 \times S^3 \times T^4$ geometries in the presence of NS-NS and RR 3-form backgrounds. We also comment on the relationship of string thermodynamics and the thermodynamic behavior of the sector of Yang-Mills theory which is the holographic dual of the string theory.Comment: 22 pages, JHEP style, minor misprints corrected, some comments adde

The interpretation of systematic reviews with meta-analyses: an objective or subjective process?

<p>Abstract</p> <p>Background</p> <p>Discrepancies between the conclusions of different meta-analyses (quantitative syntheses of systematic reviews) are often ascribed to methodological differences. The objective of this study was to determine the discordance in interpretations when meta-analysts are presented with identical data.</p> <p>Methods</p> <p>We searched the literature for all randomized clinical trials (RCT) and review articles on the efficacy of intravenous magnesium in the early post-myocardial infarction period. We organized the articles chronologically and grouped them in packages. The first package included the first RCT, and a summary of the review articles published prior to first RCT. The second package contained the second and third RCT, a meta-analysis based on the data, and a summary of all review articles published prior to the third RCT. Similar packages were created for the 5^thRCT, 10^thRCT, 20^thRCT and 23^rdRCT (all articles). We presented the packages one at a time to eight different reviewers and asked them to answer three clinical questions after each package based solely on the information provided. The clinical questions included whether 1) they believed magnesium is now proven beneficial, 2) they believed magnesium will eventually be proven to be beneficial, and 3) they would recommend its use at this time.</p> <p>Results</p> <p>There was considerable disagreement among the reviewers for each package, and for each question. The discrepancies increased when the heterogeneity of the data increased. In addition, some reviewers became more sceptical of the effectiveness of magnesium over time, and some reviewers became less sceptical.</p> <p>Conclusion</p> <p>The interpretation of the results of systematic reviews with meta-analyses includes a subjective component that can lead to discordant conclusions that are independent of the methodology used to obtain or analyse the data.</p

"Flogging dead horses": evaluating when have clinical trials achieved sufficiency and stability? A case study in cardiac rehabilitation

<p>Abstract</p> <p>Background</p> <p>Most systematic reviews conclude that another clinical trial is needed. Measures of sufficiency and stability may indicate whether this is true.</p> <p>Objectives: To show how evidence accumulated on centre-based versus home-based cardiac rehabilitation, including estimates of sufficiency and stability</p> <p>Methods</p> <p>Systematic reviews of clinical trials of home versus centre-based cardiac rehabilitation were used to develop a cumulative meta-analysis over time. We calculated the standardised mean difference (SMD) in effect, confidence intervals and indicators of sufficiency and stability. Sufficiency refers to whether the meta-analytic database adequately demonstrates that an intervention works - is statistically superior to another. It does this by assessing the number of studies with null results that would be required to make the meta-analytic effect non-statistically significant. Stability refers to whether the direction and size of the effect is stable as new studies are added to the meta-analysis.</p> <p>Results</p> <p>The standardised mean effect difference reduced over fourteen comparisons from a non-significant difference favouring home-based cardiac rehabilitation to a very small difference favouring hospital (SMD -0.10, 95% CI -0.32 to 0.13). This difference did not reach the sufficiency threshold (failsafe ratio 0.039 < 1) but did achieve the criteria for stability (cumulative slope 0.003 < 0.005).</p> <p>Conclusions</p> <p>The evidence points to a relatively small effect difference which was stable but not sufficient in terms of the suggested thresholds. Sufficiency should arguably be based on substantive significance and decided by patients. Research on patient preferences should be the priority. Sufficiency and stability measures are useful tools that need to be tested in further case studies.</p