Dynamics of HIV latency and reactivation in a primary CD4+ T cell model.

HIV latency is a major obstacle to curing infection. Current strategies to eradicate HIV aim at increasing transcription of the latent provirus. In the present study we observed that latently infected CD4+ T cells from HIV-infected individuals failed to produce viral particles upon ex vivo exposure to SAHA (vorinostat), despite effective inhibition of histone deacetylases. To identify steps that were not susceptible to the action of SAHA or other latency reverting agents, we used a primary CD4+ T cell model, joint host and viral RNA sequencing, and a viral-encoded reporter. This model served to investigate the characteristics of latently infected cells, the dynamics of HIV latency, and the process of reactivation induced by various stimuli. During latency, we observed persistence of viral transcripts but only limited viral translation. Similarly, the reactivating agents SAHA and disulfiram successfully increased viral transcription, but failed to effectively enhance viral translation, mirroring the ex vivo data. This study highlights the importance of post-transcriptional blocks as one mechanism leading to HIV latency that needs to be relieved in order to purge the viral reservoir.

Interest Rate Co-movements, Global Factors and the Long End of the Term Spread

The disconnect between rising short and low long interest rates has been a distinctive feature of the 2000s. Both research and policy circles have argued that international forces, such as global monetary policy (e.g. Rogoff, 2006); international business cycles (e.g. Borio and Filardo, 2007); or a global savings glut (e.g Bernanke, 2005) may be responsible. In this paper, we employ recent advances in panel data econometrics to document the disconnect and link it explicitly to the existence of a global latent factor that dominates the long end of the term spread for the recent period; the saving glut story emerges as the most likely contender for the global factor.

Understanding Liquidity and Credit Risks in the Financial Crisis

This paper develops a structured dynamic factor model for the spreads between London Interbank Offered Rate (LIBOR) and overnight index swap (OIS) rates for a panel of banks. Our model involves latent factors which reflect liquidity and credit risk. Our empirical results show that surges in the short term LIBOR-OIS spreads during the 2007-2009 fi nancial crisis were largely driven by liquidity risk. However, credit risk played a more signifi cant role in the longer term (twelve-month) LIBOR-OIS spread. The liquidity risk factors are more volatile than the credit risk factor. Most of the familiar events in the financial crisis are linked more to movements in liquidity risk than credit risk.

Poor and Sick: Estimating the relationship between Household Income and Health

This study evaluates the effect of the individual‘s household income on their health at the later stages of working life. A structural equation model is utilised in order to derive a composite and continuous index of the latent health status from qualitative health status indicators. The endogenous relationship between health status and household income status is taken into account by using IV estimators. The findings reveal a significant effect of individual household income on health before and after endogeneity is taken into account and after a host of other factors which is known to influence health, including hereditary factors and the individual‘s locus of control. Importantly, it is also shown that the childhood socioeconomic position of the individual has long lasting effects on health as it appears to play a significant role in determining health during the later stages of working life.

Kaposi sarcoma herpes virus antibody response and viremia following highly active antiretroviral therapy in the Swiss HIV Cohort study.

OBJECTIVE: To describe the effect of HAART on Kaposi sarcoma herpes virus (KSHV) antibody response and viremia among HIV-positive MSM. DESIGN: A follow-up study of 272 HIV-positive MSM (including 22 with Kaposi sarcoma) who first initiated HAART between January 1996 and July 2004 in the Swiss HIV Cohort Study. METHODS: For each individual, two serum samples, one at HAART initiation and another 24 months later, were tested for latent and lytic KSHV antibodies using immunofluorescence assays, and for KSHV viremia using PCR. Factors associated with changes in KSHV antibody titers and viremia were evaluated. RESULTS: At HAART initiation, 69.1 and 75.0% of patients were seropositive to latent and lytic KSHV antibodies, respectively. Seropositivity was associated with the presence of Kaposi sarcoma, older age, lower CD8 cell count and higher CD4/CD8 ratio. Prevalence of KSHV viremia at HAART initiation was 6.4%, being significantly higher among patients with Kaposi sarcoma (35.0%), and those with HIV viral loads 100 000 copies/ml (11.7%) or higher. At 24-month follow-up, geometric mean titers (GMTs) among KSHV seropositive patients increased and antibody seroprevalence was higher. Having Kaposi sarcoma and/or CD4 cell counts less than 50 cells/microl at HAART initiation was associated both with higher probability for antibody titers to increase (including seroconversion) and larger increases in GMTs. Only one of 17 viremic patients at HAART initiation had viremia at 24-month follow-up. CONCLUSION: HAART increases KSHV-specific humoral immune response and clearance of viremia among HIV-infected MSM, consistent with the dramatic protection offered by HAART against Kaposi sarcoma.

Co-movements in Real Effective Exchange Rates: Evidence from the Dynamic Hierarchical Factor Model

We analyze and quantify co-movements in real effective exchange rates while considering the regional location of countries. More specifically, using the dynamic hierarchical factor model (Moench et al. (2011)), we decompose exchange rate movements into several latent components; worldwide and two regional factors as well as country-specific elements. Then, we provide evidence that the worldwide common factor is closely related to monetary policies in large advanced countries while regional common factors tend to be captured by those in the rest of the countries in a region. However, a substantial proportion of the variation in the real exchange rates is reported to be country-specific; even in Europe country-specific movements exceed worldwide and regional common factors.

Social norms, morals and self-interest as determinants of pro-environment behaviour.

This paper considers the role which selfish, moral and social incentives and pressures play in explaining the extent to which stated choices over pro-environment behaviours vary across individuals. The empirical context is choices over household waste contracts and recycling actions in Poland. A theoretical model is used to show how cost-based motives and the desire for a positive self- and social image combine to determine the utility from alternative choices of recycling behaviour. We then describe a discrete choice experiment designed to empirically investigate the effects such drivers have on stated choices. Using a latent class model, we distinguish three types of individual who are described as duty-orientated recyclers, budget recyclers and homo oeconomicus. These groups vary in their preferences for how frequently waste is collected, and the number of categories into which household waste must be recycled. Our results have implications for the design of future policies aimed at improving participation in recycling schemes.

Les nanoparticules, une nouvelle arme contre le crime ?

Nanoparticles, a new tool to deter crime? The detection of fingermarks at a crime scene or on evidence related with a criminal affair constitutes one of the main tasks of the investigators. Fingerprints, due to their uniqueness and invariability in time, remain a key element of an identification process (being for suspects or victims). The main difficulty resides in the fact that, most of the time, fingermarks are not visible through naked eye due to their chemical composition and the small amount of material that is left on the scene. There are said to be latent and their detection requires the application of specific techniques (optical or chemical). If numerous efficient techniques currently exist, there is a continuing quest for developing new techniques or reagents with an enhanced sensitivity towards secretions and with an increased efficiency. This article gives an outline about some currently performed researches based on the use of functionalized nanoparticles to detect latent fingermarks.

Modelling Housing Prices using a Present Value State Space Model

This paper introduces a State Space approach to explain the dynamics of rent growth, expected returns and Price-Rent ratio in housing markets. According to the present value model, movements in price to rent ratio should be matched by movements in expected returns and expected rent growth. The state space framework assume that both variables follow an autoregressive process of order one. The model is applied to the US and UK housing market, which yields series of the latent variables given the behaviour of the Price-Rent ratio. Resampling techniques and bootstrapped likelihood ratios show that expected returns tend to be highly persistent compared to rent growth. The Öltered expected returns is considered in a simple predictability of excess returns model with high statistical predictability evidenced for the UK. Overall, it is found that the present value model tends to have strong statistical predictability in the UK housing markets.

Modelling Housing Prices using a Present Value State Space Model

This paper introduces a State Space approach to explain the dynamics of rent growth, expected returns and Price-Rent ratio in housing markets. According to the present value model, movements in price to rent ratio should be matched by movements in expected returns and expected rent growth. The state space framework assume that both variables follow an autoregression process of order one. The model is applied to the US and UK housing market, which yields series of the latent variables given the behaviour of the Price-Rent ratio. Resampling techniques and bootstrapped likelihood ratios show that expected returns tend to be highly persistent compared to rent growth. The filtered expected returns is considered in a simple predictability of excess returns model with high statistical predictability evidence for the UK. Overall, it is found that the present value model tends to have strong statistical predictability in the UK housing markets.

La gestió del subministrament d'aigua potable a la comarca de l'Alt Empordà

El treball tracta sobre la gestió de l’aigua a la Comarca de l’Alt Empordà i per fer-ho comença analitzant la legislació de la Unió Europea sobre gestió hidràulica i les transposicions que se n’han fet a l’estat espanyol; també es recull el que és la legislació pròpia de l’estat i la de la Comunitat Autònoma de Catalunya. En aquest darrer punt és on es comença una anàlisi més detinguda i finalment el treball es centra en la comarca de l’Alt Empordà on encara conviuen diferents maneres de gestionar l’aigua: amb xarxa mancomunada, amb pobles amb captació pròpia i alguns pobles on encara no existeix la xarxa pública d’aigua en ple segle XXI per rocambolesc que això pugui semblar. S’analitzen dins de la comarca les diferents xarxes existents, quines són les normatives que les regeixen i els seus respectius òrgans de gestió. I encara concentrant-ho més s’analitza concretament el cas de Vila-sacra (el meu poble) on la xarxa pública d’aigua es va construir tot just a partir de l’any 2003 i per tant on m’ha estat relativament fàcil seguir les passes de l’inici de l’ajuntament com a administració que s’encarrega a partir de la construcció de la xarxa, de gestionar tant la captació, com el tractament, la posterior distribució i el cobrament final d’aquesta aigua consumida pels veïns inclosos els cànons establerts per l’ACA i que després ha de liquidar a l’entitat superior. M’ha servit per analitzar quina part de la xarxa es paga amb fons municipals, quina amb la contribució dels veïns i què es considera xarxa en alta i per tant va a càrrec de l’ACA com a administració hidràulica superior a Catalunya. La conclusió del treball m’ha portat a proposar que la millor solució per una comarca especialment complicada com és l’Alt Empordà amb un gran nombre de municipis (concretament 68) seria la d’establir una xarxa mancomunada comuna a tots els municipis o potser dues si volguéssim distingir els municipis d’interior i més essencialment rurals dels de costa i que tenen una forta influència del turisme, cosa que fa que la demanda d’aigua no sigui lineal sinó que tingui pics de consum a l’estiu que és precisament l’estació més seca de l’any. En definitiva, no podem desentendre’ns d’aquest recurs tan vital perquè tots som responsables d’un ús eficient. Així, una mena d’inici d’aplicació d’aquesta solució hauria de passar per la creació d’un ens ultramunicipalista, o per exemple, aprofitar-ne un de ja creat i en ple funcionament com és la xarxa establerta pel Consorci de la Costa Brava (pels pobles de costa i turístics) i després unificar tota la resta de la comarca i que tota s’abastís directament del Pantà de Boadella. La despesa inicial de construcció de la xarxa potser seria important però el resultat analitzat amb el pas de temps necessàriament hauria de ser positiu i probablement no es tornaria a donar una situació de sequera tan crítica com la recentment viscuda, durant la qual es va arribar a aprovar un transvasament d’urgència d’aigua de l’Ebre fins a l’àrea de Barcelona. Durant aquella crisi, els embassaments van estar per sota del 30%, es van organitzar portades d’aigua en vaixell, es va restringir el reg i els usos ornamentals a les conques internes (les comarques de Barcelona, Girona i del Camp de Tarragona) i es va estar a un pas de decretar restriccions al consum humà a l’àrea de Barcelona. Aquesta situació ens va fer replantejar a tots nivells el tema del consum d’aigua i de si realment el nostre territori pot assumir o no més construcció i per tant més població o unes instal•lacions que comporten un gran consum d’aigua com per exemple més camps de golf. Un any després, el panorama és ben diferent. Els embassaments estan tots per sobre del 80%, les muntanyes dels Pirineus han acumulat durant l’hivern una generosa i inusual reserva de neu, les amenaces de restriccions han quedat enrere i els transvasaments d’aigua de les conques de l’Ebre cap a l’àrea de Barcelona, amb el conflicte polític i territorial que això comportava, han estat aparentment descartats i fora de l’agenda política del país. Però no s’ha d’oblidar que el problema continua latent.

A mega-analysis of genome-wide association studies for major depressive disorder.

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Multivariate contemporaneous-threshold autoregressive models

This paper proposes a contemporaneous-threshold multivariate smooth transition autoregressive (C-MSTAR) model in which the regime weights depend on the ex ante probabilities that latent regime-specific variables exceed certain threshold values. A key feature of the model is that the transition function depends on all the parameters of the model as well as on the data. Since the mixing weights are also a function of the regime-specific innovation covariance matrix, the model can account for contemporaneous regime-specific co-movements of the variables. The stability and distributional properties of the proposed model are discussed, as well as issues of estimation, testing and forecasting. The practical usefulness of the C-MSTAR model is illustrated by examining the relationship between US stock prices and interest rates.

Low occurrence of arthritic manifestations in patients with pulmonary tuberculosis: T cell subsets and humoral studies

Given the suspected role of mycobacteria in the establishment of disorders with an autoimmune background and joint damage, a study was conducted to analize whether rheumatic symptoms were likely to be present in tuberculosis (TB) patients. To this end, 330 patients with a bacteriologic confirmation of tuberculosis were investigated for the presence of arthritic complaints. The latter were recorded in five of them with rheumatic symptoms mostly involving interphalangeal and metacarpophalanged joints, and preceding the clinical manifestations of the TB illness. Three out of these five patients remained arthritic by the time of the bacteriologic conversion and fulfilled the criteria for the diagnosis of rheumatoid arthritis. In the two remaining patients sputum negativization was accompanied by a disappearance of rheumatic manifestations. These patients were also assessed for their peripheral levels of major T cell subsets as well as for the presence of autoantibodies. Comparisons with a series of non-arthritic TB cases, rheumatoid arthritis patients, and controls revealed that presence of rheumatic manifestations was associated with a different profile of autoantibody formation and T cell subset changes. Evidence recorded in the present study indicates that joint affectation in TB is a rare event, being rather the exception than the rule.

Use of the 2,3-diacyl-trehalose and the purified protein derivative in the serodiagnosis of tuberculosis in AIDS

The effect of the human immunodeficiency virus (HIV) infection on IgG production against purified protein derivative (PPD) and 2,3-diacil-trehalose (SL-IV) was investigated by an enzyme-linked immunosorbent assay (ELISA) test. Comparison between the antigens showed that immunocompetent patients produce preferentially antibodies to SL-IV than to PPD (73.3% versus 63.3%). Combination of these results showed an increase of the sensitivity to 80%, which decreased over the spectrum of immunodepression caused by HIV. In the tuberculous HIV seropositive group the sensitivities of SL-IV and PPD were 36.4% versus 40% and 0% versus 22.2% in the tuberculosis/acquired immunodeficiency syndrome (TB/AIDS) group. Combination of these results gave respectively 54.5% and 20%, showing that serological tests have limited value for diagnosis of tuberculosis in HIV infected patients. High antibody levels were observed in HIV seropositive asymptomatic group, but only two individuals were positive for both antigens. In the follow up, one of them developed tuberculous lymphadenitis, indicating that further work is needed to access the value of serological tests in predicting tuberculosis in HIV infected individuals.