Right ventricular outflow tract reconstruction using a valved biological conduit (Hancock conduit) late after Tetralogy of Fallot surgical correction

OBJECTIVES: The most appropriate strategy in the management of right ventricular outflow tract (RVOT) reconstruction in patients with tetralogy of Fallot early repair and late failure of right ventricle to pulmonary artery continuity is still debated. This study addresses this issue by evaluating retrospectively 12 years experience in this kind of reconstruction, focusing exclusively on the performance of Hancock conduits. METHODS: Data from 32 patients with an early repaired Tetralogy of Fallot, 23 males and 9 females, who underwent 34 RVOT reconstruction (2 were reinterventions) with Hancock conduit at Fondazione Toscana "G. Monasterio" Pediatric Cardiac Surgery department, Massa, Italy between February 2003 and May 2015 were retrospectively reviwed. Median age was 17,6 +/- 11,32 years (range 13 months to 41 years and 8 months), mean BSA 1,4 +/- 0,54m2 (0,34 m2 minimum and 2,12 m2 most), mean height 148,1 +/- 33,6 cm (range 61 cm to 195 cm) and mean weight 49,5 +/- 26,35 Kg (range 6,9 Kg to 96 Kg). The RV-PA peak gradient, RV mean pressure and pulmonary regurgitation were measured before and after the surgical conduit implantation and on follow-up, in addition RV end-diastolic volume index was measured, when feasible, before and after Hancock implantation. RESULTS: The early 30 days mortality was 6,25% and not related to conduit failure. Complete follow-up was feasible in 27 patients and the mean duration was 31,6 +/- 34,42 months. The observed RV-PA peak gradient means were 60,4 +/- 30,06 mmHg preoperatively, 29,1 +/- 11,48 mmHg postoperatively and 45,3 +/- 26,02 mmHg on the last follow-up; RV mean pressures were 53,3 +/- 27,73 mmHg preoperatively 41,6 +/- 12,71 mmHg postoperatively and 53,6 +/- 18,8 mmHg on the last follow-up; RV end-diastolic volume index means were 218,3 +/- 57,94 ml/m2 before surgery and 126,1 +/- 14,49 ml/m2 after surgery. Conduit failure was observed in 5 patients in which the the mean freedom from conduit failure was 70,56 +/- 15,02 months (mean age at failure 6,86 +/- 1,78 years), in 4 of them percutaneous intervention were attempted (2 ballooning and 2 melody), 2 successful. DISCUSSION: From our series the Hancock conduit can be actually considered as a valuable solution for RVOT reconstruction in already operated patients with ToF, considering good RV pressures and gradients values even after up to 9 years of follow up

Counting defects with the two-point correlator

We study how topological defects manifest themselves in the equal-time two-point field correlator. We consider a scalar field with Z_2 symmetry in 1, 2 and 3 spatial dimensions, allowing for kinks, domain lines and domain walls, respectively. Using numerical lattice simulations, we find that in any number of dimensions, the correlator in momentum space is to a very good approximation the product of two factors, one describing the spatial distribution of the defects and the other describing the defect shape. When the defects are produced by the Kibble mechanism, the former has a universal form as a function of k/n, which we determine numerically. This signature makes it possible to determine the kink density from the field correlator without having to resort to the Gaussian approximation. This is essential when studying field dynamics with methods relying only on correlators (Schwinger-Dyson, 2PI).Comment: 11 pages, 7 figures

A Molecular and Co-Evolutionary Context for Grazer Induced Toxin Production in Alexandrium tamarense

Marine dinoflagellates of the genus Alexandrium are the proximal source of neurotoxins associated with Paralytic Shellfish Poisoning. The production of these toxins, the toxin biosynthesis and, thus, the cellular toxicity can be influenced by abiotic and biotic factors. There is, however, a lack of substantial evidence concerning the toxins' ecological function such as grazing defense. Waterborne cues from copepods have been previously found to induce a species-specific increase in toxin content in Alexandrium minutum. However, it remains speculative in which context these species-specific responses evolved and if it occurs in other Alexandrium species as well. In this study we exposed Alexandrium tamarense to three copepod species (Calanus helgolandicus, Acartia clausii, and Oithona similis) and their corresponding cues. We show that the species-specific response towards copepod-cues is not restricted to one Alexandrium species and that co-evolutionary processes might be involved in these responses, thus giving additional evidence for the defensive role of phycotoxins. Through a functional genomic approach we gained insights into the underlying molecular processes which could trigger the different outcomes of these species-specific responses and consequently lead to increased toxin content in Alexandrium tamarense. We propose that the regulation of serine/threonine kinase signaling pathways has a major influence in directing the external stimuli i.e. copepod-cues, into different intracellular cascades and networks in A. tamarense. Our results show that A. tamarense can sense potential predating copepods and respond to the received information by increasing its toxin production. Furthermore, we demonstrate how a functional genomic approach can be used to investigate species interactions within the plankton community

Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.</p> <p>The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.</p> <p>Methods</p> <p>TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.</p> <p>Results</p> <p>Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (<it>p </it>= 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).</p> <p>Conclusion</p> <p>TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.</p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Azimuthal Anisotropy of Photon and Charged Particle Emission in Pb+Pb Collisions at 158 A GeV/c

The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in Pb + Pb collisions at 158 A GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.Comment: 8 pages and 6 figures. The manuscript has undergone a major revision. The unwanted correlations were enhanced in the random subdivision method used in the earlier version. The present version uses the more established method of division into subevents separated in rapidity to minimise short range correlations. The observed results for charged particles are in agreement with results from the other experiments. The observed anisotropy in photons is explained using flow results of pions and the correlations arising due to the decay of the neutral pion

School performance of international adoptees better than expected from cognitive test results

Objective: To investigate school performance of international adoptees in relation to their cognitive competence. Method: From the population of all male Swedish residents born 1973–1976, registered in the census 1985 and with complete test scores from military conscription, the following study groups were identified: Korean adoptees (n = 320), non-Korean adoptees (n = 1,125), siblings (children born by adoptive parents, n = 190) and Swedish majority comparisons (n = 142,024). Global scores from intelligence tests at conscription were compared with grade points from the last compulsory school year (year 9). Linear and logistic regression was applied in statistical analyses. Results: The mean grade points in theoretical subjects were lower in non-Korean adoptees than in the majority population, but when global test scores from military conscription were adjusted for, outcomes were significantly better, equal for physics, than in the majority population. The grade points of Korean adoptees were higher than in the majority population and the same held true after adjusting for global test scores. When SES was taken into account, the risk of poor school performance (only completed lower subject levels) increased in non-Korean adoptees compared to models only adjusted for age and sex. Conclusion: Male international adoptees generally perform better in school than expected by their cognitive competence. A cognitive evaluation is important in the assessment of adoptees with learning difficulties

Immunological analysis of a Lactococcus lactis-based DNA vaccine expressing HIV gp120

For reasons of efficiency Escherichia coli is used today as the microbial factory for production of plasmid DNA vaccines. To avoid hazardous antibiotic resistance genes and endotoxins from plasmid systems used nowadays, we have developed a system based on the food-grade Lactococcus lactis and a plasmid without antibiotic resistance genes. We compared the L. lactis system to a traditional one in E. coli using identical vaccine constructs encoding the gp120 of HIV-1. Transfection studies showed comparable gp120 expression levels using both vector systems. Intramuscular immunization of mice with L. lactis vectors developed comparable gp120 antibody titers as mice receiving E. coli vectors. In contrast, the induction of the cytolytic response was lower using the L. lactis vector. Inclusion of CpG motifs in the plasmids increased T-cell activation more when the E. coli rather than the L. lactis vector was used. This could be due to the different DNA content of the vector backbones. Interestingly, stimulation of splenocytes showed higher adjuvant effect of the L. lactis plasmid. The study suggests the developed L. lactis plasmid system as new alternative DNA vaccine system with improved safety features. The different immune inducing properties using similar gene expression units, but different vector backbones and production hosts give information of the adjuvant role of the silent plasmid backbone. The results also show that correlation between the in vitro adjuvanticity of plasmid DNA and its capacity to induce cellular and humoral immune responses in mice is not straight forward

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

Failure patterns and survival outcomes in triple negative breast cancer (TNBC): a 15 year comparison of 448 non-Hispanic black and white women

Purpose: Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer with unique pathologic, molecular and clinical behavior. It occurs more frequently in young blacks and has been reported to have a shorter disease-free interval. We undertook this study to analyze the demographic characteristics, failure patterns, and survival outcomes in this disease. Methods: A total of 448 non-Hispanic black and white women were identified over a 15 year period from 1996 to 2011. Demographic and clinical information including age, race, menopausal status, stage, tumor characteristics, and treatments were collected. Fisher’s exact test and multivariable Cox regression were used to compare failure patterns and survival outcomes between races. Results: 49 % (n = 223) were black. 59 % patients were between 41 and 60 years, with 18 % ≤40 years. 57 % were premenopausal and 89 % had grade 3 tumors. Stage II (47 %) was most frequent stage at diagnosis followed by stage III (28 %). 32 % had lymphovascular invasion. Adjusting for age, stage, and grade, there was no difference in survival outcomes (OS, DFS, LFFS, and DFFS) between the two races. 62 (14 %) patients failed locally either in ipsilateral breast or chest wall, and 19 (4 %) failed in the regional lymphatics. Lung (18 %) was the most frequent distant failure site with <12 % each failing in brain, liver and bones. Conclusion: Failure patterns and survival outcomes did not differ by race in this large collection of TNBC cases. Lung was the predominate site of distant failure followed by brain, bone, and liver. Few patients failed in the regional lymphatics