Single-equation tests for cointegration with GLS detrended data

We provide GLS-based versions of two widely used approaches for testing whether or not non-stationary economic time series are cointegrated: single-equation static re- gression or residual-based tests and single-equation conditional error correction model (ECM) based tests. Our approach is to consider nearly optimal tests for unit roots and apply them in the cointegration context. Our GLS versions of the tests do in- deed provide substantial improvements over their OLS counterparts. We derive the local asymptotic power functions of all tests considered for a DGP with weakly ex- ogenous regressors. This allows obtaining the relevant non-centrality parameter to quasi-di§erence the data. We investigate the e§ect of non-weakly exogenous regressors via simulations. With weakly exogenous regressors strongly correlated with the depen- dent variable, the ECM tests are clearly superior. When the regressors are potentially non-weakly exogenous, the residuals-based tests are clearly preferred

Residuals-based tests for cointegration with generalized least-squares detrended data

We provide generalized least-squares (GLS) detrended versions of single-equation static regression or residuals-based tests for testing whether or not non-stationary time series are cointegrated. Our approach is to consider nearly optimal tests for unit roots and to apply them in the cointegration context. We derive the local asymptotic power functions of all tests considered for a triangular data-generating process, imposing a directional restriction such that the regressors are pure integrated processes. Our GLS versions of the tests do indeed provide substantial power improvements over their ordinary least-squares counterparts. Simulations show that the gains in power are important and stable across various configurations

GLS Detrending, Efficient Unit Root Tests and Structural Change

We extend the class of M-tests for a unit root analyzed by Perron and Ng (1996) and Ng and Perron (1997) to the case where a change in the trend function is allowed to occur at an unknown time. These tests M(GLS) adopt the GLS detrending approach of Dufour and King (1991) and Elliott, Rothenberg and Stock (1996) (ERS). Following Perron (1989), we consider two models : one allowing for a change in slope and the other for both a change in intercept and slope. We derive the asymptotic distribution of the tests as well as that of the feasible point optimal tests PT(GLS) suggested by ERS. The asymptotic critical values of the tests are tabulated. Also, we compute the non-centrality parameter used for the local GLS detrending that permits the tests to have 50% asymptotic power at that value. We show that the M(GLS) and PT(GLS) tests have an asymptotic power function close to the power envelope. An extensive simulation study analyzes the size and power in finite samples under various methods to select the truncation lag for the autoregressive spectral density estimator. An empirical application is also provided.Nous généralisons la classe de M-tests pour racine unitaire analysés par Perron et Ng (1996) et Ng et Perron (1997) au cas où la fonction de tendance peut avoir une rupture à une date inconnue. Ces tests M(GLS) utilisent la méthode des moindres carrés généralisés (MCG) pour éliminer les composantes déterministes, tel que proposé par Dufour et King (1991) et Elliot, Rothenberg et Stock (1996) (ERS). Suivant Perron (1989), nous considérons deux modèles : le premier permet une rupture dans la pente et le deuxième un changement d'ordonnée à l'origine (en plus de la rupture de la pente). Nous dérivons la distribution asymptotique des tests MGLS et celle d'une version réalisable du test optimal en un point PT(GLS) suggéré par ERS. Nous calculons aussi les valeurs critiques de ces tests. De plus, nous calculons le paramètre de non-centralité (utilisé dans l'estimation MCG pour éliminer les composantes déterministes) qui permet d'atteindre une puissance asymptotique de 50 %. Nous montrons que les tests M(GLS) et PT(GLS) ont des fonctions de puissance asymptotique proches de l'enveloppe de puissance. En utilisant des simulations, nous évaluons le niveau et la puissance des tests en échantillons finis et nous étudions plusieurs méthodes pour sélectionner le retard nécessaire pour calculer l'estimateur autorégressif de la densité spectrale. Une application à des séries de salaires réels et aux prix des actions ordinaires aux Etats-Unis est aussi considérée à la fin

Changes in toxin production of environmental Pseudomonas aeruginosa isolates exposed to sub-inhibitory concentrations of three common antibiotics

Pseudomonas aeruginosa is an environmental pathogen that can cause severe infections in immunocompromised patients. P. aeruginosa infections are typically treated with multiple antibiotics including tobramycin, ciprofloxacin, and meropenem. However, antibiotics do not always entirely clear the bacteria from the infection site, where they may remain virulent. This is because the effective antibiotic concentration and diffusion in vitro may differ from the in vivo environment in patients. Therefore, it is important to understand the effect of non-lethal sub-inhibitory antibiotic concentrations on bacterial phenotype. Here, we investigate if sub-inhibitory antimicrobial concentrations cause alterations in bacterial virulence factor production using pyocyanin as a model toxin. We tested this using the aforementioned antibiotics on 10 environmental P. aeruginosa strains. Using on-the-spot electrochemical screening, we were able to directly quantify changes in production of pyocyanin in a measurement time of 17 seconds. Upon selecting 3 representative strains to further test the effects of sub-minimum inhibitory concentration (MICs), we found that pyocyanin production changed significantly when the bacteria were exposed to 10-fold MIC of the 3 antibiotics tested, and this was strain specific. A series of biologically relevant measured pyocyanin concentrations were also used to assess the effects of increased virulence on a culture of epithelial cells. We found a decreased viability of the epithelial cells when incubated with biologically relevant pyocyanin concentrations. This suggests that the antibiotic-induced virulence also is a value worth being enclosed in regular testing of pathogens

Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, $\beta$-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, $\beta$-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes.Organismic and Evolutionary Biolog

Biomedical Ph.D. Students Enrolled in Two Elite Universities in the United Kingdom and the United States Report Adopting Multiple Learning Relationships

Objective: The ability to form multiple learning relationships is a key element of the doctoral learning environment in the biomedical sciences. Of these relationships, that between student and supervisor has long been viewed as key. There are, however, limited data to describe the student perspective on what makes this relationship valuable. In the present study, we discuss the findings of semi-structured interviews with biomedical Ph.D. students from the United Kingdom and the United States to: i) determine if the learning relationships identified in an Australian biomedical Ph.D. cohort are also important in a larger international student cohort; and ii) improve our understanding of student perceptions of value in their supervisory relationships. Study Design 32 students from two research intensive universities, one in the United Kingdom (n = 17), and one in the United States (n = 15) were recruited to participate in a semi-structured interview. Verbatim transcripts were transcribed, validated and analysed using a Miles and Huberman method for thematic analysis. Results: Students reported that relationships with other Ph.D. students, post-doctoral scientists and supervisors were all essential to their learning. Effective supervisory relationships were perceived as the primary source of high-level project guidance, intellectual support and confidence. Relationships with fellow students were viewed as essential for the provision of empathetic emotional support. Technical learning was facilitated, almost exclusively, by relationships with postdoctoral staff. Conclusions: These data make two important contributions to the scholarship of doctoral education in the biomedical sciences. Firstly, they provide further evidence for the importance of multiple learning relationships in the biomedical doctorate. Secondly, they clarify the form of a ‘valued’ supervisory relationship from a student perspective. We conclude that biomedical doctoral programs should be designed to contain a minimum level of formalised structure to promote the development of multiple learning relationships that are perceived as key to student learning

Income inequality, gene expression, and brain maturation during adolescence

Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regional variations relate to those in glucocorticoid receptor (HPA) and androgen receptor (HPG) gene expression. For each sex, we used a median split of income inequality and household income (income-to-needs ratio) to create four subgroups. In female adolescents, the high-inequality low-income group displayed the greatest age-related decreases in cortical thickness. In this group, expression of glucocorticoid and androgen receptor genes explained the most variance in these age-related decreases in thickness across the cortex. We speculate that female adolescents living in high-inequality neighborhoods and low-income households may experience greater HPA and HPG activity, leading to steeper decreases in cortical thickness with age

Prenatal exposure to maternal cigarette smoking, amygdala volume, and fat intake in adolescence

Context : Prenatal exposure to maternal cigarette smoking is a well-established risk factor for obesity, but the underlying mechanisms are not known. Preference for fatty foods, regulated in part by the brain reward system, may contribute to the development of obesity. Objective : To examine whether prenatal exposure to maternal cigarette smoking is associated with enhanced fat intake and risk for obesity, and whether these associations may be related to subtle structural variations in brain regions involved in reward processing. Design : Cross-sectional study of a population-based cohort. Setting : The Saguenay Youth Study, Quebec, Canada. Participants : A total of 378 adolescents (aged 13 to 19 years; Tanner stage 4 and 5 of sexual maturation), half of whom were exposed prenatally to maternal cigarette smoking (mean [SD], 11.1 [6.8] cigarettes/d). Main Outcome Measures : Fat intake was assessed with a 24-hour food recall (percentage of energy intake consumed as fat). Body adiposity was measured with anthropometry and multifrequency bioimpedance. Volumes of key brain structures involved in reward processing, namely the amygdala, nucleus accumbens, and orbitofrontal cortex, were measured with magnetic resonance imaging. Results : Exposed vs nonexposed subjects exhibited a higher total body fat (by approximately 1.7 kg; P = .009) and fat intake (by 2.7%; P = .001). They also exhibited a lower volume of the amygdala (by 95 mm3; P < .001) but not of the other 2 brain structures. Consistent with its possible role in limiting fat intake, amygdala volume correlated inversely with fat intake (r = −0.15; P = .006). Conclusions : Prenatal exposure to maternal cigarette smoking may promote obesity by enhancing dietary preference for fat, and this effect may be mediated in part through subtle structural variations in the amygdala

Growth of white matter in the adolescent brain: role of testosterone and androgen receptor

The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath

Orbitofrontal cortex and drug use during adolescence : role of prenatal exposure to maternal smoking and BDNF genotype

Context : Prenatal exposure to maternal cigarette smoking (PEMCS) may affect brain development and behavior in adolescent offspring. Objective : To evaluate the involvement of the orbitofrontal cortex (OFC) in mediating the relationship between PEMCS and substance use. Design : Cross-sectional analyses from the Saguenay Youth Study aimed at evaluating the effects of PEMCS on brain development and behavior among adolescents. Nonexposed adolescents were matched with adolescents exposed prenatally to cigarette smoking by maternal educational level. Participants and Setting : A French Canadian founder population of the Saguenay–Lac-Saint-Jean region of Quebec, Canada.The behavioral data set included 597 adolescents (275 sibships; 12-18 years of age), half of whom were exposed in utero to maternal cigarette smoking. Analysis of cortical thickness and genotyping were performed using available data from 314 adolescents. Main Outcome Measures : The likelihood of substance use was assessed with the Diagnostic Interview Schedule for Children Predictive Scales. The number of different drugs tried by each adolescent was assessed using another questionnaire. Thickness of the OFC was estimated from T1-weighted magnetic resonance images using FreeSurfer software. Results : Prenatal exposure to maternal cigarette smoking is associated with an increased likelihood of substance use. Among exposed adolescents, the likelihood of drug experimentation correlates with the degree of OFC thinning. In nonexposed adolescents, the thickness of the OFC increases as a function of the number of drugs tried. The latter effect is moderated by a brain-derived neurotrophic factor (BDNF) genotype (Val66Met). Conclusions : We speculate that PEMCS interferes with the development of the OFC and, in turn, increases the likelihood of drug use among adolescents. In contrast, we suggest that, among nonexposed adolescents, drug experimentation influences the OFC thickness via processes akin to experience-induced plasticity