Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)

Background: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample.Results: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace.Conclusion: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed.

Preliminary report of the first season work of the International Pluridisciplinary Archaeological Expedition to Bactria 2007

A prior long-term and complex evaluation of the already available data on the geophysical prospecting during the first season work carried out at 2006, at the archaeological site of Tchinguiz Tepe of Termez, took place to decide the strategy to follow during the campaign of 2007. This previous evaluation of the information, on one hand, leaded to the decision to increase the geophysical prospecting at Tchinguiz Tepe, on the other hand, to decide the exact location of areas where the archaeological interventions.would carry out. The main objective at the beginning of this new season was to crosscheck the reliabilityof the measurements and, at the same time, to establish the unknown up to the present archaeologicaland chronological sequence of Tchinguiz Tepe. Meanwhile, the geophysical prospecting also wasextended to the outskirts of the city were the localisation of an unknown up to now Buddhist Monasterywas possible.

Estudi del procés de neurodegeneració

Les anomenades malalties neurodegeneratives tenen una simptomatologia i unes manifestacions clíniques molt diferents entre elles. No obstant, totes elles convergeixen en el mateix procés final, la neurodegeneració, que es manifestarà en diferents localitzacions o tipus cel·lulars del sistema nerviós. Nosaltres, plantegem la hipòtesi de que els processos moleculars i cel·lulars subjacents a la neurodegeneració són comuns per totes elles. Després de dur a terme un procés de selecció, es decideix treballar amb la malaltia de Parkinson, la d’Alzheimer, l’Esclerosi lateral amiotròfica i l’esclerosi múltiple. Hem pogut determinar que hi ha set processos moleculars o cel·lulars que estan associats al procés de neurodegeneració i que són comuns a totes elles. Havent-les estudiat per separat s’observa que el procés de neurodegeneració consisteix en una fallada en cadena de diferents sistemes moleculars i cel·lulars que tenen com a punt d’origen l’estrès oxidatiu. A aquest estrès s’hi pot arribar de diferents maneres. Una d’elles és l’exposició excessiva a certs metalls, que provoca la pèrdua dels sistemes antioxidants cel·lulars. Degut a això, els mitocondris reben un impacte oxidatiu massa gran i comencen a fallar. El fet que aquest orgànul actuï com a tampó del calci intracel·lular en provoca la seva desregulació, alterant d’aquesta manera el senyal nerviós. En resposta a l’estrès oxidatiu i tèrmic que genera la disfunció mitocondrial, s’activen les Proteïnes de Xoc Tèrmic (HSP) que actuant de citocines i presentadores d’antígens, inicien la resposta immunològica contra les cèl·lules danyades. Paral·lelament, s’observa un increment de la permeabilitat de la barrera hematoencefàlica degut a la pèrdua de les adhesions cel·lulars estretes per l’alta presència d’espècies reactives. Com a conseqüència de l’afebliment o el trencament de la barrera hematoencefàlica, es pot produir una entrada al SNC de diferents substàncies neurotòxiques i de cèl·lules del sistema immunitàri que, en condicions normals tenen l’accés restringit. Juntament amb aquestes cèl·lules immunològiques, també s’activen les cèl·lules del sistema immunitari innat residents al cervell, la micròglia, i totes elles secreten citocines proinflamatòries que contribueixen al procés de neurodegeneració. Nosaltres presentem els mecanismes pels quals aquesta inflamació, lluny d’atenuar-se, es cronifica per l’acció de certs bucles de retroalimentació positiva. Les diferents peculiaritats de cada malaltia contribueixen en aquest procés de diferents maneres, com és el cas dels pèptids β-amilides en la malaltia d’Alzheimer, l’α-sinucleina en el Parkinson, la superòxid dismutasa (SOD) en l’esclerosi lateral amiotròfica, o l’infiltració de leucòcits al cervell degut a la resposta autoimmune de l’esclerosi múltiple.Deixant de banda aquestes diferències, si el procés és comú entre totes elles, l’estudi a fons d’aquest procés hauria de poder permetre identificar dianes tarapèutiques que siguin comunes per les quatre malalties.

The maximum voltage drop in an on-chip power distribution network: analysis of square, triangular and hexagonal power pad arrangements

A mathematical model of the voltage drop which arises in on-chip power distribution networks is used to compare the maximum voltage drop in the case of different geometric arrangements of the pads supplying power to the chip. These include the square or Manhattan power pad arrangement, which currently predominates, as well as equilateral triangular and hexagonal arrangements. In agreement with the findings in the literature and with physical and SPICE models, the equilateral triangular power pad arrangement is found to minimize the maximum voltage drop. This headline finding is a consequence of relatively simple formulas for the voltage drop, with explicit error bounds, which are established using complex analysis techniques, and elliptic functions in particular.

Statistical Reviewers Improve Reporting in Biomedical Articles: a Randomized Trial.

Background. Although peer review is widely considered to be the most credible way of selecting manuscripts and improving the quality of accepted papers in scientific journals, there is little evidence to support its use. Our aim was to estimate the effects on manuscript quality of either adding a statistical peer reviewer or suggesting the use of checklists such as CONSORT or STARD to clinical reviewers or both. Methodology and Principal Findings. Interventions were defined as 1) the addition of a statistical reviewer to the clinical peer review process, and 2) suggesting reporting guidelines to reviewers; with"no statistical expert" and"no checklist" as controls. The two interventions were crossed in a 262 balanced factorial design including original research articles consecutively selected, between May 2004 and March 2005, by the Medicina Clinica (Barc) editorial committee. We randomized manuscripts to minimize differences in terms of baseline quality and type of study (intervention, longitudinal, cross-sectional, others). Sample-size calculations indicated that 100 papers provide an 80% power to test a 55% standardized difference. We specified the main outcome as the increment in quality of papers as measured on the Goodman Scale. Two blinded evaluators rated the quality of manuscripts at initial submission and final post peer review version. Of the 327 manuscripts submitted to the journal, 131 were accepted for further review, and 129 were randomized. Of those, 14 that were lost to follow-up showed no differences in initial quality to the followed-up papers. Hence, 115 were included in the main analysis, with 16 rejected for publication after peer review. 21 (18.3%) of the 115 included papers were interventions, 46 (40.0%) were longitudinal designs, 28 (24.3%) cross-sectional and 20 (17.4%) others. The 16 (13.9%) rejected papers had a significantly lower initial score on the overall Goodman scale than accepted papers (difference 15.0, 95% CI: 4.6- 24.4). The effect of suggesting a guideline to the reviewers had no effect on change in overall quality as measured by the Goodman scale (0.9, 95% CI: 20.3+2.1). The estimated effect of adding a statistical reviewer was 5.5 (95% CI: 4.3-6.7), showing a significant improvement in quality. Conclusions and Significance. This prospective randomized study shows the positive effect of adding a statistical reviewer to the field-expert peers in improving manuscript quality. We did not find a statistically significant positive effect by suggesting reviewers use reporting guidelines.

Estudi de l'ensenyament-aprenentatge de la multiplicació de fraccions

Aquest treball és una investigació de com cal ensenyar la multiplicació de fraccions a l’Educació Primària. S’han recollit les dades a través d’entrevistes per conèixer com 6 mestres ensenyaven aquest coneixement matemàtic per comparar-ho amb el que diuen diferents autors com Van de Walle, Tipps, Tucker i Bruner. L’ensenyamentaprenentatge de la multiplicació de fraccions és un procés difícil i complex. Per adquirir aquest coneixement, els infants necessiten tenir experiències amb diferents situacions que es plantegi el producte de fraccions i deduir ells mateixos estratègies i algorismes propis per resoldre-les. Si se’ls dóna directament l’algorisme tradicional sense comprensió, tindran dificultats per identificar si el resultat és coherent o no.

Aprenentatge esportiu: com influeix la conducta de l’entrenador en el procés d’aprenentatge de l’esportista

Les persones estem en constant desenvolupament i socialització, i cada context en el qual ens veiem involucrats té sobre nosaltres el poder de modificar les nostres conductes. El criteri de partida és que el context esportiu també exerceix aquest domini sobre els individus que hi participen, motiu pel qual en aquest treball es pretén estudiar la influència de certs factors en el desenvolupament de la pràctica esportiva. De manera més detallada, l’objectiu que es busca és estudiar la influència conductual de l’entrenador en el procés d’aprenentatge de l’esportista. A partir d’aquest estudi s’obtindrà un perfil de com ha de ser un bon entrenador i les condicions que s’han de donar en l’esportista perquè els aprenentatges esdevinguin significatius, la qual cosa portarà a la funcionalitat i la millora del rendiment esportiu.

The Role of Firm Size in Training Provision Decisions: evidence from Spain

The level of training provided by small firms to their employees is below that provided by their larger counterparts. The provision of firm-related training is believed to be associated to certain characteristics of the firm. In this paper we argue that small firms provide fewer training opportunities as they are less likely to be associated with these characteristics than large firms. The suitability of estimating training decisions as a double-decision process is examined here: first, a firm has to decide whether to provide training or not and, second, having decided to do so, the amount of training to provide. The differences in training provision between small and large firms are decomposed in order to analyse the individual contribution of these characteristics to explaining the gap. The results show that small firms face greater obstacles in accessing training and that the main reasons for that are related to their technological activity and the geographical scope of the market in which they operate.

The maximum voltage drop in an on-chip power distribution network: analysis of square, triangular and hexagonal power pad arrangements

A mathematical model of the voltage drop which arises in on-chip power distribution networks is used to compare the maximum voltage drop in the case of different geometric arrangements of the pads supplying power to the chip. These include the square or Manhattan power pad arrangement, which currently predominates, as well as equilateral triangular and hexagonal arrangements. In agreement with the findings in the literature and with physical and SPICE models, the equilateral triangular power pad arrangement is found to minimize the maximum voltage drop. This headline finding is a consequence of relatively simple formulas for the voltage drop, with explicit error bounds, which are established using complex analysis techniques, and elliptic functions in particular.

Selecting Scientific Papers for Publication via Citation Auctions

The scientific community has been suffering from peer review for decades. This process (also called refereeing) subjects an author's scientific work or ideas to the scrutiny of one or more experts in the field. Publishers use it to select and screen manuscript submissions, and funding agencies use it to award research funds. The goal is to get authors to meet their discipline's standards and thus achieve scientific objectivity. Publications and awards that haven't undergone peer review are often regarded with suspicion by scholars and professionals in many fields. However, peer review, although universally used, has many drawbacks. We propose replacing peer review with an auction-based approach: the better the submitted paper, the more scientific currency the author likely bid to have it published. If the bid correctly reflects the paper's quality, the author is rewarded in this new scientific currency; otherwise, the author loses this currency. We argue that citations are an appropriate currency for all scientists. We believe that citation auctions encourage scientists to better control their submissions' quality. It also inspire them to prepare more exciting talks for accepted papers and to invite discussion of their results at congresses and conferences and among their colleagues. In the long run, citation auctions could have the power to greatly improve scientific research

The process of basic training, applied training, maintaining the performance of an observer

In the field of observational methodology the observer is obviously a central figure, and close attention should be paid to the process through which he or she acquires, applies, and maintains the skills required. Basic training in how to apply the operational definitions of categories and the rules for coding, coupled with the opportunity to use the observation instrument in real-life situations, can have a positive effect in terms of the degree of agreement achieved when one evaluates intra- and inter-observer reliability. Several authors, including Arias, Argudo, & Alonso (2009) and Medina and Delgado (1999), have put forward proposals for the process of basic and applied training in this context. Reid y De Master (1982) focuses on the observer's performance and how to maintain the acquired skills, it being argued that periodic checks are needed after initial training because an observer may, over time, become less reliable due to the inherent complexity of category systems. The purpose of this subsequent training is to maintain acceptable levels of observer reliability. Various strategies can be used to this end, including providing feedback about those categories associated with a good reliability index, or offering re-training in how to apply those that yield lower indices. The aim of this study is to develop a performance-based index that is capable of assessing an observer's ability to produce reliable observations in conjunction with other observers.

Ecological conflicts and valuation - mangroves vs. shrimp in the late 1990s

Shrimps are produced in two different ways. They are fished in the sea (sometimes at the cost of turtle destruction) or they are "farmed" in ponds in coastal areas. Such aquaculture is increasing around the world as shrimps become a valuable item of world trade. Mangrove forests are sacrificed for commercial shrimp farming. This paper considers the conflict between mangrove conservation and shrimp exports in different countries.Who has title to the mangroves, who wins and who loses in this tragedy of enclosures? Which languages of valuation are used by different actors in order to compare the increase in shrimp exports and the losses in livelihoods and in environmental services? The economic valuation of damages is only one of the possible languages of valuation which are relevant in practice. Who has the power to impose a particular language of valuation?

Environmental conflicts, environmental justice and valuation

In this article some historical and contemporary environmental conflicts are described. The international environmental liability of mining corporations is discussed. Comparisons are made with conflicts in the United States and in South Africa which fall under the rubric of the Environmental Justice movement. Such conflicts are fought out in many languages, and the economic valuation of damages is only one of such languages. Who has the power to impose particular languages of valuation? Who rules over the ways and means of simplifying complexity, deciding that some points of view are out of order? Who has power to determine which is the bottom-line in an environmental discussion?

Bidding for the surplus: realizing efficient outcomes in general economic environments

In this paper, we consider two classes of economic environments. In the first type, agents are faced with the task of providing local public goods that will benefit some or all of them. In the second type, economic activity takes place via formation of links. Agents need both to both form a network and decide how to share the output generated. For both scenarios, we suggest a bidding mechanism whereby agents bid for the right to decide upon the organization of the economic activity. The subgame perfect equilibria of this game generate efficient outcomes.

Personal relations and their effect on behavior in an organizational setting: an experimental study

We study how personal relations affect performance in organizations. In the experimental game we use a manager has to assign different degrees of decision power to two employees. These two employees then have to make distributive decisions which affect themselves and the manager. Our focus is on the effects on managers' assignment of decision power and on employees' distributive decisions of one of the employees and the manager knowing each other personally. Our evidence shows that managers tend to favor employees that they personally know and that these employees tend, more than other employees, to favor the manager in their distributive decisions. However, this behavior does not affect the performance of the employees that do not know the manager. All these effects are independent of whether the employees that know the manager are more or less productive than those who do not know the manager. The results shed light on discrimination and nepotism and its consequences for the performance of family firms and other organizations.