Tax smoothing in a business cycle model with capital-skill complementarity

This paper undertakes a normative investigation of the quantitative properties of optimal tax smoothing in a business cycle model with state contingent debt, capital-skill complementarity, endogenous skill formation and stochastic shocks to public consumption as well as total factor and capital equipment productivity. Our main finding is that an empirically relevant restriction which does not allow the relative supply of skilled labour to adjust in response to aggregate shocks, signi cantly changes the cyclical properties of optimal labour taxes. Under a restricted relative skill supply, the government fi nds it optimal to adjust labour income tax rates so that the average net returns to skilled and unskilled labour hours exhibit the same dynamic behaviour as under fl exible skill supply.

A stepwise protocol to coat aAPC beads prevents out-competition of anti-CD3 mAb and consequent experimental artefacts.

Artificial antigen-presenting cells (aAPC) are widely used for both clinical and basic research applications, as cell-based or bead-based scaffolds, combining immune synapse components of interest. Adequate and controlled preparation of aAPCs is crucial for subsequent immunoassays. We reveal that certain proteins such as activatory anti-CD3 antibody can be out-competed by other proteins (e.g. inhibitory receptor ligands such as PDL1:Fc) during the coating of aAPC beads, under the usually performed coating procedures. This may be misleading, as we found that decreased CD8 T cell activity was not due to inhibitory receptor triggering but rather because of unexpectedly low anti-CD3 antibody density on the beads upon co-incubation with inhibitory receptor ligands. We propose an optimized protocol, and emphasize the need to quality-control the coating of proteins on aAPC beads prior to their use in immunoassays.

Esclerose de varizes do esôfago em pacientes esquistossomóticos

To assess the therapeutic possibilities of injection sclerosis in schistosomotic portal hypertension, a 5-year prospective study was conducted in northeast Brazil, where this parasitosis is endemic. Fifty patients undergoing endoscopy for upper gastrointestinal hemorrage from rupture of esophageal varices from July through December 1981 were chosen for the study. The 32 consenting patients were submitted to injection sclerotherapy paravariceally, using ethanolamine oleate; the 18 refusing to participate were assigned to the control group. The incidence of rebleeding was 28.1% in the former and 44.5% in the latter, a difference wich was not statistically significant (Fisher's test, p = 0.017). Since sclerotherapymarkedly improved the long-term survival rate of the patients, this procedure is advocated for the treatment of esophageal varices in cases of portal hypertension due to schistosomiasis.

Bayesian classification criterion for forensic multivariate data

This study presents a classification criteria for two-class Cannabis seedlings. As the cultivation of drug type cannabis is forbidden in Switzerland, law enforcement authorities regularly ask laboratories to determine cannabis plant's chemotype from seized material in order to ascertain that the plantation is legal or not. In this study, the classification analysis is based on data obtained from the relative proportion of three major leaf compounds measured by gas-chromatography interfaced with mass spectrometry (GC-MS). The aim is to discriminate between drug type (illegal) and fiber type (legal) cannabis at an early stage of the growth. A Bayesian procedure is proposed: a Bayes factor is computed and classification is performed on the basis of the decision maker specifications (i.e. prior probability distributions on cannabis type and consequences of classification measured by losses). Classification rates are computed with two statistical models and results are compared. Sensitivity analysis is then performed to analyze the robustness of classification criteria.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.

OBJECTIVE: To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy. PATIENTS AND METHODS: This was a multicenter, open-label, single-arm, exploratory, phase II clinical trial. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST). The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. RESULTS: Twenty pretreated SCLC patients (median age, 60 years) with extensive (n=13) or limited-stage disease (n=7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2). Objective tumor responses were not observed and only one of the 17 evaluable patients had SD. With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively. The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase. CONCLUSION: This clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC. One patient died due to multi-organ failure. The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.

Taxes de reincidència 2009 de justícia juvenil: actualització de la taxa de reincidència dels joves sotmesos a mesures de llibertat vigilada i internament en centre

Taxes de reincidència 2009 de justícia juvenil: actualització de la taxa de reincidència dels joves sotmesos a mesures de llibertat vigilada i internament en centre L’estudi actualitza les taxes de reincidència dels menors sotmesos a una mesura d’internament o de llibertat vigilada que van ser publicades a la recerca “La reincidència en el delicte en la justícia de menors” finalitzada l’any 2005 i que van iniciar la sèrie. Aquest estudi ja és el cinquè del mateix tipus i, en aquest cas, segueix els joves que van finalitzar una mesura de llibertat vigilada o d’internament l’any 2006, i els segueix fins el 31 de desembre de 2009 amb l’objectiu de saber si han comès un nou delicte que hagi estat detectat per la Xarxa d’execució penal, tant de joves com d’adults. S’ha estudiat tota la població de joves desinternats de centres, que per l’any 2006 foren 169 subjectes. En el cas de llibertat vigilada del total de joves que finalitzaren mesura l’any 2006 (N=1.017), s’ha fet una mostra de 525 subjectes (interval de confiança:95,5%; marge d’error ±3,04; p=q=50) Els resultats en llibertat vigilada apunten a un augment en la taxa de reincidència (28,8%) aquest darrer any. Aquest augment s’explica en part per la incorporació al Codi Penal dels delictes de trànsit, on els joves han fet un creixement espectacular que no hi era als anys anteriors. En canvi, en internament la taxa de reincidència ha baixat 12 punts respecte l’any anterior i és la més baixa de totes les recollides en les series fetes fins ara (50,3%). L’estudi permet comparar de forma seriada ja cinc anys d’evolució de la taxa de reincidència juvenil després de la posada en marxa de la Llei Orgànica 5/2000, de 12 de gener, reguladora de la responsabilitat penal dels menors (LORPM). Updated recidivism rates of juveniles after serving supervised freedom or custodial sentences (2009) The study updates juvenile recidivism rates in Catalonia (following an annual series that has been published during the last 4 years). The sample is compounded by juveniles after serving a penal measure (supervised freedom or custodial sentences). In this case, the young population (14-18 years old) that finished a penal measure in 2006 was followed until December 31, 2009. The results show an increasing rate of recidivism in the case of youngsters submitted to the community measure called supervised freedom (28.8%), while recidivism related to custodial sentences decrease 12 points (50.3%) Tasas de reincidencia 2009 de justicia juvenil. Actualización de la tasa de reincidencia de los jóvenes sometidos a medidas de libertad vigilada e internamiento en centro El estudio actualiza por cuarto año las tasas de reincidencia juvenil en las medidas de libertad vigilada e internamiento en Catalunya. En este caso se ha estudiado a la población que finalizó una medida el año 2006 y se les ha seguido hasta el 31 de diciembre de 2009. Los resultados nos dicen que aumenta la tasa de reincidencia de libertad vigilada (28,8%) y desciende de manera significativa en 12 puntos la de internamiento (50,3%)

Tasas de reincidencia 2009 de justicia juvenil : Actualización de la tasa de reincidencia de los jóvenes sometidos a medidas de libertad vigilada e internamiento en centro

El estudio actualiza por cuarto año las tasas de reincidencia juvenil en las medidas de libertad vigilada e internamiento en Catalunya. En este caso se ha estudiado a la población que finalizó una medida el año 2006 y se les ha seguido hasta el 31 de diciembre de 2009. Los resultados nos dicen que aumenta la tasa de reincidencia de libertad vigilada (28,8%) y desciende de manera significativa en 12 puntos la de internamiento (50,3%) L’estudi actualitza les taxes de reincidència dels menors sotmesos a una mesura d’internament o de llibertat vigilada que van ser publicades a la recerca “La reincidència en el delicte en la justícia de menors” finalitzada l’any 2005 i que van iniciar la sèrie. Aquest estudi ja és el cinquè del mateix tipus i, en aquest cas, segueix els joves que van finalitzar una mesura de llibertat vigilada o d’internament l’any 2006, i els segueix fins el 31 de desembre de 2009 amb l’objectiu de saber si han comès un nou delicte que hagi estat detectat per la Xarxa d’execució penal, tant de joves com d’adults. S’ha estudiat tota la població de joves desinternats de centres, que per l’any 2006 foren 169 subjectes. En el cas de llibertat vigilada del total de joves que finalitzaren mesura l’any 2006 (N=1.017), s’ha fet una mostra de 525 subjectes (interval de confiança:95,5%; marge d’error ±3,04; p=q=50) Els resultats en llibertat vigilada apunten a un augment en la taxa de reincidència (28,8%) aquest darrer any. Aquest augment s’explica en part per la incorporació al Codi Penal dels delictes de trànsit, on els joves han fet un creixement espectacular que no hi era als anys anteriors. En canvi, en internament la taxa de reincidència ha baixat 12 punts respecte l’any anterior i és la més baixa de totes les recollides en les series fetes fins ara (50,3%). L’estudi permet comparar de forma seriada ja cinc anys d’evolució de la taxa de reincidència juvenil després de la posada en marxa de la Llei Orgànica 5/2000, de 12 de gener, reguladora de la responsabilitat penal dels menors (LORPM). Updated recidivism rates of juveniles after serving supervised freedom or custodial sentences (2009) The study updates juvenile recidivism rates in Catalonia (following an annual series that has been published during the last 4 years). The sample is compounded by juveniles after serving a penal measure (supervised freedom or custodial sentences). In this case, the young population (14-18 years old) that finished a penal measure in 2006 was followed until December 31, 2009. The results show an increasing rate of recidivism in the case of youngsters submitted to the community measure called supervised freedom (28.8%), while recidivism related to custodial sentences decrease 12 points (50.3%)

Prevention of transfusional Trypanosoma cruzi infection in Latin America

Trypanosoma cruzi is a protozoan infection widely spread in Latin America, from Mexico in the north to Argentina and Chile in the south. The second most important way of acquiring the infection is by blood transfusion. Even if most countries of Latin America have law/decree/norms, that make mandatory the screening of blood donors for infectious diseases, including T. cruzi (El Salvador and Nicaragua do not have laws on the subject), there is usually no enforcement or it is very lax. Analysis of published serologic surveys of T. cruzi antibodies in blood donors done in 1993, indicating the number of donors and screening coverage for T. cruzi in ten countries of Central and South America indicated that the probability of receiving a potentially infected transfusion unit in each country varied from 1,096 per 10,000 transfusions in Bolivia, the highest, to 13.02 or 13.86 per 10,000 transfusions in Honduras and Venezuela respectively, where screening coverage was 100%. On the other hand the probability of transmitting a T. cruzi infected unit was 219/10,000 in Bolivia, 24/10,000 in Colombia, 17/10,000 in El Salvador, and around 2-12/10,000 for the seven other countries. Infectivity risks defined as the likelihood of being infected when receiving an infected transfusion unit were assumed to be 20% for T. cruzi. Based on this, estimates of the absolute number of infections induced by transfusion indicated that they were 832, 236, and 875 in Bolivia, Chile and Colombia respectively. In all the other countries varied from seven in Honduras to 85 in El Salvador. Since 1993, the situation has improved. At that time only Honduras and Venezuela screened 100% of donors, while seven countries, Argentina, Colombia, El Salvador, Honduras, Paraguay, Uruguay and Venezuela, did the same in 1996. In Central America, without information from Guatemala, the screening of donors for T. cruzi prevented the transfusion of 1,481 infected units and the potential infection of 300 individuals in 1996. In the same year, in seven countries of South America, the screening prevented the transfusion of 36,017 infected units and 7, 201 potential cases of transfusional infection.

Association of CYP3A5 genotypes with blood pressure and renal function in African families.

OBJECTIVE: Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families. METHODS: Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations. RESULTS: CYP3A5*1 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A5*1 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A5*1 carriers (P for interaction = 0.02). CONCLUSIONS: These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium- related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling.

Anemia en pacientes de edad avanzada con insuficiencia cardíaca ingresados en un servicio de medicina interna

Introducción: la anemia es una entidad muy prevalente en pacientes con insuficiencia cardíaca (IC) y se asocia a mayor morbimortalidad. Objetivos: analizar las comorbilidades de pacientes hospitalizados de ≥ 65 años con IC. Estudiar el impacto de la anemia sobre esta población y comparar esta comorbilidad respecto a aquéllos que no la presentan en relación a la valoración geriátrica integral (VGI), así como la adecuación del tratamiento farmacológico en la IC. Pacientes y métodos: estudio descriptivo observacional transversal de una cohorte de 150 pacientes ingresados en el Servicio de Medicina Interna del Hospital Vall d’Hebron, entre junio de 2007 y enero de 2010, mediante entrevista clínica y recogida de datos de la historia clínica. Resultados: en la muestra prevalecían las mujeres (62%), los pacientes con hipertensión (84%), los que tenían la FEVI conservada (66,4%) y los pacientes con anemia (61,3%), de los cuales el 60,9% presentaban anemia inflamatoria y el 35,9% anemia ferropénica. Los pacientes con anemia tuvieron peor valor de MNA (p=0,017, con un RR de 2,7), mayor diferencial de Barthel (p=0,021) y peor valor de albuminemia (p=0,001). Asimismo, se observó que 53 pacientes con indicación según las guías clínicas de tratamiento con IECA o ARA II no lo seguían, y hasta 105 pacientes en el caso de los betabloqueantes (BB). Conclusiones: los pacientes con anemia presentaban pero estado nutricional, y mayor empeoramiento del índice de Barthel. Respecto al tratamiento de la IC, destacaba el gran número de pacientes sin tratamiento con IECA, ARA II o BB, que deberían llevarlo según las guías de práctica clínica.

Different epitopes of the LACK protein are recognized by V beta 4 V alpha 8 CD4+ T cells in H-2b and H-2d mice susceptible to Leishmania major.

After inoculation of Leishmania major, a rapid production of IL-4 by LACK-specific CD4+ T cells has been shown to drive Th2 cell development in susceptible mice i.e. BALB/c and C57BL/6 mice rendered susceptible by neutralization of IFN-gamma at the onset of infection. Here, we showed that peptide AA 156-173 induced an early IL-4 mRNA expression not only in BALB/c mice but also in resistant B10.D2 mice when IFN-gamma is neutralized. Epitope mapping of LACK protein demonstrated that peptide containing AA 293-305 induced early IL-4 mRNA transcripts in susceptible H-2b mice i.e. BALB/b and resistant C57BL/6 mice when IFN-gamma is neutralized. Stringently, the early IL-4 response to the H-2d (AA 156-173) or the H-2b (AA 293-305) epitopes occurred in V beta 4 V alpha 8 CD4+ T cells from either H-2d or H-2b susceptible mice, respectively.

Involvement of nuclear factor-kappaB in macrophage migration inhibitory factor gene transcription up-regulation induced by interleukin- 1 beta in ectopic endometrial cells.

OBJECTIVE: To investigate the involvement of the nuclear factor (NF)-kappaB in the interleukin (IL)-1 beta-mediated macrophage migration inhibitory factor (MIF) gene activation. DESIGN: Prospective study. SETTING: Human reproduction research laboratory. PATIENT(S): Nine women with endometriotic lesions. INTERVENTION(S): Endometriotic lesions were obtained during laparoscopic surgery. MAIN OUTCOME MEASURE(S): The MIF protein secretion was analyzed by ELISA, MIF mRNA expression by quantitative real-time polymerase chain reaction (PCR), NF-kappaB translocation into the nucleus by electrophoresis mobility shift assay, I kappaB phosphorylation and degradation by Western blot, and human MIF promoter activity by transient cell transfection. RESULT(S): This study showed a significant dose-dependent increase of MIF protein secretion and mRNA expression, the NF-kappaB translocation into the nucleus, I kappaB phosphorylation, I kappaB degradation, and human MIF promoter activity in endometriotic stromal cells in response to IL-1 beta. Curcumin (NF-kappaB inhibitor) significantly inhibited all these IL-1 beta-mediated effects. Analysis of the activity of deletion constructs of the human MIF promoter and a computer search localized two putative regulatory elements corresponding to NF-kappaB binding sites at positions -2538/-2528 bp and -1389/-1380 bp. CONCLUSION(S): This study suggests the involvement of the nuclear transcription factor NF-kappaB in MIF gene activation in ectopic endometrial cells in response to IL-1 beta and identifies a possible pathway of endometriosis-associated inflammation and ectopic cell growth.