The Effect of Restricting Asset Trade in Dynamic Equilibrium Models

This paper shows that differences between the predictions of an international real business cycle model with complete markets and the predictions of a model where agentscan only trade rsk-free bonds depend heavily on the calibrated values for the degree of persistence in productivity shocks, the discount factor and the degree of international spillovers in productivity shocks. Since empirical work yields point estimates of the degrees of persistence and spillovers in productiv- ity shocks that bear large standard errors, the outcomes of quantitative studies using only the point estimates of these parameters inherit the substantial uncertainty associated with the empirical estimates.

Labour Market Dynamics in RBC Models

This paper explores the ability of a large set of RBC type models to explain aggregate US data by examining how well the rst-order conditions (FOCs) from each model t the data. Typically, the residuals from the FOC for hours worked are large in magnitude (more volatile than total hours), very highly persistent, and stay away from zero for long periods of time. This pattern suggests that standard RBC models are unable to capture the dynamics in the joint behaviour of consumption, output and hours that exists in the US data. We show that models which generate dynamic terms in the FOC for hours worked are able to capture this feature of the data by exploring a RBC model augmented by learning by doing which has been shown to have such a dynamic FOC. The results are remarkable. The residuals from the hours FOC are much less volatile than total hours and display no persistence. Less conclusive results emerge from models with habit formation in preferences which also yield dynamic FOCs for the labour input. We conclude that an additional dynamic component in the FOCs is essential to better capture the dynamics in the data and future research using the RBC structure should explore models that deliver it.

Note sur l’aire de distribution et l’importance du Dacnusa dryas, un parasite introduit au Québec pour lutter contre l’agromyze de la lyzerne (Agromyza frontella)

De 1978 à 1980, le Dacnusa dryas, un hyménoptère d'origine européenne parasitant les larves et les pupes de l'agromyze de la luzerne, Agromyza frontella, fut relâché successivement dans deux localités du Québec. Une étude détaillée de son aire de distribution effectuée en 1986 démontre que l'insecte s'est dispersé dans les douze régions agricoles du Québec. Suite à sa naturalisation, les populations d'agromyze ont diminué à des niveaux sous-économiques.Dacnusa dryas, a European larval-pupal parasitoid of the alfalfa blotch leafminer, Agromyza frontella, was successively released in two areas of Quebec from 1978 to 1980. A detailed survey in 1986 shows that it has become established in all 12 agricultural regions. Coincident with its successful colonization, populations of the host have declined to subeconomic levels

Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.

HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer's disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181 and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181 to characterize HAND

Semi-Parametric Predictions of the Intertemporal Approach to the Current Account

This paper uses dunamic programming by GMM (DM by GMM) to solve a dynamic model of a small-open economy calibrated to Canada. The predicted paths for consumption, output, investment and trade balance (over output) are highly correlated with thier historical counterparts. Moreover, the variance of the predicted trade balance- output ratio matches the variance observed in the data. The latter result contrasts with earier research on the intertemporal approach to the current account using linear-quadratic modeals that found that the sample paths for the current account predicted by the theory are less volatile than the historical paths in Canadian data. It is shown that a special case of the model with a constant world interest rate does not match the historical path of the trade balance as well.

ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects.

BackgroundDolutegravir (DTG), a once-daily, human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF).MethodsING116070 is an ongoing, single-arm, open-label, multicenter study in antiretroviral therapy-naive, HIV-1-infected adults. Subjects received DTG (50 mg) plus abacavir/lamivudine (600/300 mg) once daily. The CSF and plasma (total and unbound) DTG concentrations were measured at weeks 2 and 16. The HIV-1 RNA levels were measured in CSF at baseline and weeks 2 and 16 and in plasma at baseline and weeks 2, 4, 8, 12, and 16.ResultsThirteen white men enrolled in the study; 2 withdrew prematurely, 1 because of a non-drug-related serious adverse event (pharyngitis) and 1 because of lack of treatment efficacy. The median DTG concentrations in CSF were 18 ng/mL (range, 4-23 ng/mL) at week 2 and 13 ng/mL (4-18 ng/mL) at week 16. Ratios of DTG CSF to total plasma concentration were similar to the unbound fraction of DTG in plasma. Median changes from baseline in CSF (n = 11) and plasma (n = 12) HIV-1 RNA were -3.42 and -3.04 log10 copies/mL, respectively. Nine of 11 subjects (82%) had plasma and CSF HIV-1 RNA levels <50 copies/mL and 10 of 11 (91%) had CSF HIV-1 RNA levels <2 copies/mL at week 16.ConclusionsThe DTG concentrations in CSF were similar to unbound plasma concentrations and exceeded the in vitro 50% inhibitory concentration for wild-type HIV (0.2 ng/mL), suggesting that DTG achieves therapeutic concentrations in the central nervous system. The HIV-1 RNA reductions were similar in CSF and plasma. Clinical Trials Registration. NCT01499199

CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS

No abstract available

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria.

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes

Efavirenz Is Predicted To Accumulate in Brain Tissue: an In Silico, In Vitro, and In Vivo Investigation

Adequate concentrations of efavirenz in the central nervous system (CNS) are necessary to suppress viral replication, but high concentrations may increase the likelihood of CNS adverse drug reactions. The aim of this investigation was to evaluate the efavirenz distribution in the cerebrospinal fluid (CSF) and the brain by using a physiologically based pharmacokinetic (PBPK) simulation for comparison with rodent and human data. The efavirenz CNS distribution was calculated using a permeability-limited model on a virtual cohort of 100 patients receiving efavirenz (600 mg once daily). Simulation data were then compared with human data from the literature and with rodent data. Wistar rats were administered efavirenz (10 mg kg of body weight(−1)) once daily over 5 weeks. Plasma and brain tissue were collected for analysis via liquid chromatography-tandem mass spectrometry (LC-MS/MS). The median maximum concentrations of drug (C(max)) were predicted to be 3,184 ng ml(−1) (interquartile range [IQR], 2,219 to 4,851 ng ml(−1)), 49.9 ng ml(−1) (IQR, 36.6 to 69.7 ng ml(−1)), and 50,343 ng ml(−1) (IQR, 38,351 to 65,799 ng ml(−1)) in plasma, CSF, and brain tissue, respectively, giving a tissue-to-plasma ratio of 15.8. Following 5 weeks of oral dosing of efavirenz (10 mg kg(−1)), the median plasma and brain tissue concentrations in rats were 69.7 ng ml(−1) (IQR, 44.9 to 130.6 ng ml(−1)) and 702.9 ng ml(−1) (IQR, 475.5 to 1,018.0 ng ml(−1)), respectively, and the median tissue-to-plasma ratio was 9.5 (IQR, 7.0 to 10.9). Although it is useful, measurement of CSF concentrations may give an underestimation of the penetration of antiretrovirals into the brain. The limitations associated with obtaining tissue biopsy specimens and paired plasma and CSF samples from patients make PBPK modeling an attractive tool for probing drug distribution