Generation of induced pluripotent stem cells from human cord blood cells with only two factors:OCT4 and SOX2

Induced pluripotent stem cells (iPSC ) provide an invaluable resource for regenerative medicine as they allow the generationof patient-specific progenitors with potential value for cell therapy. However, in many instances, an off-the-shelf approach isdesirable, such as for cell therapy of acute conditions or when the patient’s somatic cells are altered as a consequence of a chronicdisease or aging. Cord blood (CB) stem cells appear ideally suited for this purpose as they are young cells expected to carryminimal somatic mutations and possess the immunological immaturity of newborn cells; additionally, several hundred thousandimmunotyped CB units are readily available through a worldwide network of CB banks. Here we present a detailed protocol for thederivation of CB stem cells and how they can be reprogrammed to pluripotency by retroviral transduction with only two factors(OCT 4 and SO X2) in 2 weeks and without the need for additional chemical compounds.

Taxation of banks: a theoretical framework

The goal of this paper is to develop a model of financial intermediation analyze the impact of various forms of taxation. The model considers in a unified framework various functions of banks: monitoring, transaction services and asset transformation. Particular attention is devoted to conditions for separability between deposits and loans. The analysis focuses on: (i) competition between banks and alternative financial arrangements (investment funds and organized security markets), (ii) regulation, and (iii) bank's monopoly power and risk taking behavior.

An analysis of strategic paths through the decomposition of total factor productivity: the case of Spanish savings banks

The Spanish savings banks attracted quite a considerable amount of interest within the scientific arena, especially subsequent to the disappearance of the regulatory constraints during the second decade of the 1980s. Nonetheless, a lack of research identified with respect to mainstream paths given by strategic groups, and the analysis of the total factor productivity. Therefore, on the basis of the resource-based view of the firm and cluster analysis, we make use of changes in structure and performance ratios in order to identify the strategic groups extant in the sector. We attain a threeways division, which we link with different input-output specifications defining strategic paths. Consequently, on the basis of these three dissimilar approaches we compute and decompose a Hicks-Moorsteen total factor productivity index. Obtained results put forward an interesting interpretation under a multi-strategic approach, together with the setbacks of employing cluster analysis within a complex strategic environment. Moreover, we also propose an ex-post method of analysing the outcomes of the decomposed total factor productivity index that could be merged with non-traditional techniques of forming strategic groups, such as cognitive approaches.

When do central banks prefer to intervene secretly?

Central banks often intervene secretly in the foreign exchange market. This secrecy seems to be at odds with the signalling channel. In this article we will analyse when a central bank intervening in the foreign exchange rate market purely through the signalling channel would prefer to act secretly or publicly. By using a microstructure model, we will show that the consistency of the intervention with fundamentals, the volume of noise trading, the weight given to the effectiveness of intervention and the degree of superior information held by the central bank will influence the decision to intervene secretly or publicly. Keywords: foreign exchange intervention, market microstructure. JEL Classifi…cation: D82, E58, F31, G14.

Lowering blood alcohol content levels to save lives: The european experience

Road safety has become an increasing concern in developed countries due to the significant amount of mortal victims and the economic losses derived. Only in 2005 these losses rose to 200.000 million euros, a significant amount - approximately the 2% of its GDP- that easily justifies any public intervention. One tool used by governments to face this challenge is the enactment of stricter policies and regulations. Since drunk driving is one of the most important concerns of public authorities on this field, several European countries decided to lower their illegal Blood Alcohol Content levels to 0.5 mg/ml during the last decade. This study evaluates for the first time the effectiveness of this transition using European panel-based data (CARE) for the period 1991-2003 using the Differences-in-Differences method in a fixed effects estimation that allows for any pattern of correlation (Cluster-Robust). My results show the existence of positive impacts on certain groups of road users and for the whole population when the policy is accompanied by some enforcement interventions. Moreover, a time lag of more than two years is found in that effectiveness. Finally, I also assert the importance of controlling for serial correlation in the evaluation of this kind of policies.

Differential time to positivity of blood cultures: a valid method for diagnosing catheter-related bloodstream infections in the intensive care unit

iii. Catheter-related bloodstream infection (CR-BSI) diagnosis usually involves catheter withdrawal. An alternative method for CR-BSI diagnosis is the differential time to positivity (DTP) between peripheral and catheter hub blood cultures. This study aims to validate the DTP method in short-term catheters. The results show a low prevalence of CR-BSI in the sample (8.4%). The DTP method is a valid alternative for CR-BSI diagnosis in those cases with monomicrobial cultures (80% sensitivity, 99% specificity, 92% positive predictive value, and 98% negative predictive value) and a cut-off point of 17.7 hours for positivity of hub blood culture may assess in CR-BSI diagnosis.

Clinical application of differential time to positivity of blood cultures as a diagnostic method for catheter-related bloodstream infection.

La sospita de bacterièmia relacionada a catèter (BRC) necessita la retirada d’aquest, confirmant-se a posteriori només en un 15-25%. La diferencia en el temps de positivització d´ hemocultius (DTP) ha demostrat ser un mètode fiable per el diagnòstic de BRC evitant la retirada del catèter. Amb la intenció de comprovar la utilitat clínica de la DTP, l’hem comparada amb un mètode diagnòstic estàndard. Hem inclòs 133 pacients ingressats a una unitat de cures intensives portadors de catèters venosos centrals. 56 pacients s’han aleatoritzats. No hem trobat diferències significatives en quant a morbi-mortalitat en els 2 grups havent evitat 70% de retirada innecessària de catèters en el grup de DTP.

Modelling the cardiovascular system for automatic interpretation of the blood pressure curve

A four compartment model of the cardiovascular system is developed. To allow for easy interpretation and to minimise the number of parameters, an effort was made to keep the model as simple as possible. A sensitivity analysis is first carried out to determine which are the most important model parameters to characterise the blood pressure signal. A four stage process is then described which accurately determines all parameter values. This process is applied to data from three patients and good agreement is shown in all cases.

Estimating arterial blood gases with the EABC® System (“Earlobe Arterialized Blood Collector”) in critically ill patients. A validation study.

The Earlobe Arterialized Blood Collector® is a minimally invasive system able to perform arterialized capillary blood gas analysis from the earlobe (EL). A prospective validation study was performed in 55 critical ill patients. Sampling failure rate was high (53.6%). Risk factors were age > 65 years, diabetes, vasoactive drug therapy and noradrenaline (NA) doses above 0.22 μg / kg / min. Multivariate analysis showed age > 65 years was the only factor independently associated with failure. Concordance analysis with arterial blood gases and Bland-Altman agreement evaluation were insufficient for validating the new system for all gasometrical variables.

Blood levels of brain-derived neurotrophic factor correlate with several psychopathological symptoms in anorexia nervosa patients

Background: Evidence of a role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of eating disorders (ED) has been provided by association studies and by murine models. BDNF plasma levels have been found altered in ED and in psychiatric disorders that show comorbidity with ED. Aims: Since the role of BDNF levels in ED-related psychopathological symptoms has not been tested, we investigatedthe correlation of BDNF plasma levels with the Symptom Checklist 90 Revised (SCL-90R) questionnaire in a total of 78 ED patients. Methods: BDNF levels, measured bythe enzyme-linked immunoassay system, and SCL-90R questionnaire, were assessed in a total of 78 ED patients. The relationship between BDNF levels and SCL-90R scales was calculated using a general linear model. Results: BDNF plasma levels correlated with the Global Severity Index and the Positive Symptom Distress Index global scales and five of the nine subscales in the anorexia nervosa patients. BDNF plasma levels were able to explain, in the case of the Psychoticism subscale, up to 17% of the variability (p = 0.006). Conclusion: Our data suggest that BDNF levels could be involved in the severity of the disease through the modulation of psychopathological traits that are associated with the ED phenotype.

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

Genetic characterization of the ABO blood group in Neandertals

Background: The high polymorphism rate in the human ABO blood group gene seems to be related to susceptibility to different pathogens. It has been estimated that all genetic variation underlying the human ABO alleles appeared along the human lineage, after the divergence from the chimpanzee lineage. A paleogenetic analysis of the ABO blood group gene in Neandertals allows us to directly test for the presence of the ABO alleles in these extinct humans. Results: We have analysed two male Neandertals that were retrieved under controlled conditions at the El Sidron site in Asturias (Spain) and that appeared to be almost free of modern human DNA contamination. We find a human specific diagnostic deletion for blood group O (O01 haplotype) in both Neandertal individuals. Conclusion: These results suggest that the genetic change responsible for the O blood group in humans predates the human and Neandertal divergence. A potential selective event associated with the emergence of the O allele may have therefore occurred after humans separated from their common ancestor with chimpanzees and before the human-Neandertal population divergence.

Banks and development: Jewish communities in the Italian Renaissance and current economic performance

Are differences in local banking development long-lasting? Do they affect long-term economic performance?I answer these questions by relying on an historical development that occurred in Italian cities during the 15thcentury. A sudden change in the Catholic doctrine had driven the Jews toward money lending. Cities thatwere hosting Jewish communities developed complex banking institutions for two reasons: first, the Jews werethe only people in Italy who were allowed to lend for a profit and, second, the Franciscan reaction to Jewishusury led to the creation of charity lending institutions, the Monti di Pietà, that have survived until today andhave become the basis of the Italian banking system. Using Jewish demography in 1500 as an instrument, Iprovide evidence of (1) an extraordinary persistence in the level of banking development across Italian cities (2)large effects of current local banking development on per-capita income. Additional firm-level analyses suggestthat well-functioning local banks exert large effects on aggregate productivity by reallocating resources towardmore efficient firms. I exploit the expulsion of the Jews from the Spanish territories in Italy in 1541 to arguethat my results are not driven by omitted institutional, cultural and geographical characteristics. In particular,I show that, in Central Italy, the difference in current income between cities that hosted Jewish communitiesand cities that did not exists only in those regions that were not Spanish territories in the 16th century.

Banks, liquidity crises and economic growth

How do the liquidity functions of banks affect investment and growth at different stages ofeconomic development? How do financial fragility and the costs of banking crises evolve with the level of wealth of countries? We analyze these issues using an overlapping generations growth model where agents, who experience idiosyncratic liquidity shocks, can invest in a liquid storage technology or in a partially illiquid Cobb Douglas technology. By pooling liquidity risk, banks play a growth enhancing role in reducing inefficient liquidation of long term projects, but they may face liquidity crises associated with severe output losses. We show that middle income economies may find optimal to be exposed to liquidity crises, while poor and rich economies have more incentives to develop a fully covered banking system. Therefore, middle income economies could experience banking crises in the process of their development and, as they get richer, they eventually converge to a financially safe long run steady state. Finally, the model replicates the empirical fact of higher costs of banking crises for middle income economies.

Banks, government bonds, and default: what do the data say?

We use data from Bankscope to analyze the holdings of public bonds by over 18,000 banks located in 185 countries and the role of these bonds in 18 sovereign debt crises over the period 1998-2012. We find that: (i) banks hold a sizeable share of their assets in government bonds (about 9% on average), particularly in less financially developed countries; (ii) during sovereign crises, banks on average increase their bondholdings by 1% of their assets, but this increase is concentrated among larger and more profitable banks, and; (iii) the correlation between a bank's holdings of public bonds and its future loans is positive in normal times, but turns negative during defaults. A 10% increase in bank bond-holdings during default is associated with a 3.2% reduction in future loans, and bonds bought in normal times account for 75% of this effect. Our results are consistent with the view that there is a liquidity benefit for banks to hold public bonds in normal times, which is critical for understanding bank fragility during sovereign crises.