Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies

Background: Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics. Objective: To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias. Design, Setting, and Participants: A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArrayH NT Cycler. Outcome Measurements and Statistical Analysis: Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer. Results and Limitations: We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics. Conclusion: Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.

Persistence of tracer in the application site -a potential confounding factor in nerve regeneration studies

Selective reinnervation of peripheral targets after nerve injury might be assessed by injecting a first tracer in a target before nerve injury to label the original neuronal population, and applying a second tracer after the regeneration period to label the regenerated population. However, altered uptake of tracer, fading, and cell death may interfere with the results. Furthermore, if the first tracer injected remains in the target tissue, available for 're-uptake' by misdirected regenerating axons, which originally innervated another region, then the identification of the original population would be confused. With the aim of studying this problem, the sciatic nerve of adult rats was sectioned and sutured. After 3 days, to allow the distal axon to degenerate avoiding immediate retrograde transport, one of the dyes: Fast Blue (FB), Fluoro-Gold (FG) or Diamidino Yellow (DY), was injected into the tibial branch of the sciatic nerve, or in the skin of one of the denervated digits. Rats survived 2-3 months. The results showed labelled dorsal root ganglion (DRG) cells and motoneurones, indicating that late re-uptake of a first tracer occurs. This phenomenon must be considered when the model of sequential labelling is used for studying the accuracy of peripheral reinnervation.

Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

BACKGROUND: Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue. AIMS: To investigate whether higher BMI increases the risk of major depression. METHOD: Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI. RESULTS: Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62). CONCLUSIONS: Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Competitor comparison: variable speed drives in pumping applications

As the world’s energy demand is increasing, a durable solution to control it is to improve the energy efficiency of the processes. It has been estimated that pumping applications have a significant potential for energy savings trough equipment or control system changes. For many pumping application the use of a variable speed drive as a process control element is the most energy efficient solution. The main target of this study is to examine the energy efficiency of a drive system that moves the pump. In a larger scale the purpose of this study is to examine how the different manufacturers’ variable speed drives are functioning as a control device of a pumping process. The idea is to compare the drives from a normal pump user’s point of view. The things that are mattering for the pump user are the efficiency gained in the process and the easiness of the use of the VSD. So some thought is given also on valuating the user-friendliness of the VSDs. The VSDs are compared to each other also on the basis of their life cycle energy costs in different kind of pumping cases. The comparison is made between ACS800 from ABB, VLT AQUA Drive from Danfoss, NX-drive from Vacon and Micromaster 430 from Siemens. The efficiencies are measured in power electronics laboratory in the Lappeenranta University of Technology with a system that consists of a variable speed drive, an induction motor with dc-machine, two power analyzers and a torque transducer. The efficiencies are measured as a function of a load at different frequencies. According to measurement results the differences between the measured system efficiencies on the actual working area of pumping are on average few percent units. When examining efficiencies at the whole range of different loads and frequencies, the differences get bigger. At low frequencies and loads the differences between the most efficient and the least efficient systems are at the most about ten percent units. At the most of the tested points ABB’s drive seem to have slightly better efficiencies than the other drives.

Determinants of Broadband Access: Is Platform Competition always the Key Variable to Success?

Previous studies have identified the rivalry among technological platforms as one of the main driving forces of broadband services penetration. This paper draws on data from the Spanish market between 2005 and 2011 to estimate the main determinants of broadband prices. Controlling for broadband tariffs features and network variables, we examine the impact of the different modes of competition on prices. We find that inter-platform competition has no significant effects over prices, while intra-platform competition is a key driver of the prices charged in the broadband market. Our analysis suggests that the impact of different types of competition on prices is critically affected by the levels of development of the broadband market achieved by the considered country

Identifying variable gamma-ray sources through radio observations

We present preliminary results of a campaign undertaken with different radio interferometers to observe a sample of the most variable unidentified EGRET sources. We expect to detect which of the possible counterparts of the gamma-ray sources (any of the radio emitters in the field) varies in time with similar timescales as the gamma-ray variation. If the gamma-rays are produced in a jet-like source, as we have modelled theoretically, synchrotron emission is also expected at radio wavelengths. Such radio emission should appear variable in time and correlated with the gamma-ray variability.

Developing of the Variable Speed Drive -control in simulated parallel pumping systems

This thesis presents briefly the basic operation and use of centrifugal pumps and parallel pumping applications. The characteristics of parallel pumping applications are compared to circuitry, in order to search analogy between these technical fields. The purpose of studying circuitry is to find out if common software tools for solving circuit performance could be used to observe parallel pumping applications. The empirical part of the thesis introduces a simulation environment for parallel pumping systems, which is based on circuit components of Matlab Simulink —software. The created simulation environment ensures the observation of variable speed controlled parallel pumping systems in case of different controlling methods. The introduced simulation environment was evaluated by building a simulation model for actual parallel pumping system at Lappeenranta University of Technology. The simulated performance of the parallel pumps was compared to measured values of the actual system. The gathered information shows, that if the initial data of the system and pump perfonnance is adequate, the circuitry based simulation environment can be exploited to observe parallel pumping systems. The introduced simulation environment can represent the actual operation of parallel pumps in reasonably accuracy. There by the circuitry based simulation can be used as a researching tool to develop new controlling ways for parallel pumps.

Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

Classification models for neurocognitive impairment in HIV infection based on demographic and clinical variables

Objective: We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection. Methods: The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to btain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients. Results: The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes). Conclusion: Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.

Anàlisi de la gestió de fons d’inversió de renda variable en el període 2009-2013

La crisi financera que es va originar l’any 2007 va tenir uns efectes devastadors a tots els àmbits de l’economia. El mercat hipotecari es va desplomar i l’accés al crèdit es va restringir a la majoria de la població. Els efectes que va tenir la crisi sobre aquests mercats han estat analitzats i estudiats repetidament en diverses assignatures. Però el que es vol observar amb la realització d’aquest treball són els efectes que va provocar la crisi econòmica sobre un altre àmbit del mercat financer, el mercat de fons d’estalvi i més concretament, en el de fons d’inversió. Aquest treball vol analitzar si els mercats espanyol i europeu de fons d’inversió ha patit els efectes de la crisi econòmica i si ha estat així, en quin grau s’han vist afectats. Aquests mercats venen regits per experts professionals en la matèria i la rendibilitat d’aquests actius vindrà determinada per la gestió que aquests facin. Per poder mesurar si la seva gestió aconsegueix millorar els resultats que podríem obtenir invertint en el mercat, utilitzarem uns índexs financers anomenats mesures de performance. Dins el ventall disponible de fons d’inversió, ens centrarem en el mercat de renda variable ja que és el que presenta major variabilitat i està més sotmès a possibles canvis en el mercat. En concret s’analitzaran els resultats de la gestió del mercat de fons d’inversió de renda variable durant els anys posteriors a la crisi fins a l’actualitat tant al mercat espanyol com al mercat europeu per diferents categories de fons.

Combining conservative and variable markers to inferthe evolutionary history of Prunus subgen. Amygdalus s.l.under domestication

The genus Prunus L. is large and economically important. However, phylogenetic relationships within Prunus at low taxonomic level, particularly in the subgenus Amygdalus L. s.l., remain poorly investigated. This paper attempts to document the evolutionary history of Amygdalus s.l. and establishes a temporal framework, by assembling molecular data from conservative and variable molecular markers. The nuclear s6pdh gene in combination with the plastid trnSG spacer are analyzed with bayesian and maximum likelihood methods. Since previous phylogenetic analysis with these markers lacked resolution, we additionally analyzed 13 nuclear SSR loci with the δµ2 distance, followed by an unweighted pair group method using arithmetic averages algorithm. Our phylogenetic analysis with both sequence and SSR loci confirms the split between sections Amygdalus and Persica, comprising almonds and peaches, respectively. This result is in agreement with biogeographic data showing that each of the two sections is naturally distributed on each side of the Central Asian Massif chain. Using coalescent based estimations, divergence times between the two sections strongly varied when considering sequence data only or combined with SSR. The sequence-only based estimate (5 million years ago) was congruent with the Central Asian Massif orogeny and subsequent climate change. Given the low level of differentiation within the two sections using both marker types, the utility of combining microsatellites and data sequences to address phylogenetic relationships at low taxonomic level within Amygdalus is discussed. The recent evolutionary histories of almond and peach are discussed in view of the domestication processes that arose in these two phenotypically-diverging gene pools: almonds and peaches were domesticated from the Amygdalus s.s. and Persica sections, respectively. Such economically important crops may serve as good model to study divergent domestication process in close genetic pool.

Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants-including variants that do not reach genome-wide significance-often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).

Effect of tow-drop gaps on the damage resistance and tolerance of Variable-Stiffness Panels

This paper presents an experimental study of the effects of tow-drop gaps in Variable Stiffness Panels under drop-weight impact events. Two different configurations, with and without ply-staggering, have been manufactured by Automated Fibre Placement and compared with their baseline counterpart without defects. For the study of damage resistance, three levels of low velocity impact energy are generated with a drop-weight tower. The damage area is analysed by means of ultrasonic inspection. Results of the analysed defect configurations indicate that the influence of gap defects is only relevant under small impact energy values. However, in the case of damage tolerance, the residual compressive strength after impact does not present significant differences to that of conventional straight fibre laminates. This indicates that the strength reduction is driven mainly by the damage caused by the impact event rather than by the influence of manufacturing-induced defects

Variable-stiffness composite panels: Defect tolerance under in-plane tensile loading

Automated Fiber Placement is being extensively used in the production of major composite components for the aircraft industry. This technology enables the production of tow-steered panels, which have been proven to greatly improve the structural efficiency of composites by means of in-plane stiffness variation and load redistribution. However, traditional straight-fiber architectures are still preferred. One of the reasons behind this is related to the uncertainties, as a result of process-induced defects, in the mechanical performance of the laminates. This experimental work investigates the effect of the fiber angle discontinuities between different tow courses in a ply on the un-notched and open-hole tensile strength of the laminate. The influence of several manufacturing parameters are studied in detail. The results reveal that 'ply staggering' and '0% gap coverage' is an effective combination in reducing the influence of defects in these laminates