Trinity College

It is now quite common to have panels in which both T, the number of time series observations, and N, the number of groups, are quite large and of the same order of magnitude. The usual practice is either to estimate N separate regressions and calculate the coefficient means, which we call the mean group (MG) estimator, or to pool the data and assume that the slope coefficients and error variances are identical. In this article we propose an intermediate procedure, the pooled mean group (PMG) estimator, which constrains long-run coefficients to be identical but allows short-run coefficients and error variances to differ across groups. We consider both the case where the regressors are stationary and the case where they follow unit root processes, and for both cases derive the asymptotic distribution of the PMG estimators as T tends to infinity. We also provide two empirical applications: Aggregate consumption functions for 24 Organization for Economic Cooperation and Development economies over the period 1962–1993, and energy demand functions for 10 Asian developing economies over the period 1974–1990.

This article considers testing the hypothesis that errors in a panel data model are weakly cross-sectionally dependent, using the exponent of cross-sectional dependence α, introduced recently in Bailey, Kapetanios, and Pesaran (2012). It is shown that the implicit null of the cross-sectional dependence (CD) test depends on the relative expansion rates of N and T. When T = O(N ε), for some 0 < ε ≤1, then the implicit null of the CD test is given by 0 ≤ α < (2 − ε)/4, which gives 0 ≤ α <1/4, when N and T tend to infinity at the same rate such that T/N → κ, with κ being a finite positive constant. It is argued that in the case of large N panels, the null of weak dependence is more appropriate than the null of independence which could be quite restrictive for large panels. Using Monte Carlo experiments, it is shown that the CD test has the correct size for values of α in the range [0, 1/4], for all combinations of N and T, and irrespective of whether the panel contains lagged values of the dependent variables, so long as there are no major asymmetries in the error distribution.

Abstract The investigation of a preceding paper has shown that the temperature variation of viscosity, as determined experimentally, can be satisfactorily explained in many gases on the assumption that the repulsive and attractive parts of the molecular field are each according to an inverse power of the distance. In some cases, in argon, for example, it was further shown that the experimental facts can be explained by more than one molecular model, from which we inferred that viscosity results alone are insufficient to determine precisely the nature of molecular fields. The object of the present paper is to ascertain whether a molecular model of the same type will also explain available experimental data concerning the equation of state of a gas, and if so, whether the results so obtained, when taken in conjunction with those obtained from viscosity, will definitely fix the molecular field. Such an investigation is made possible by the elaborate analysis by Kamerlingh Onnes of the observational material. He has expressed the results in the form of an empirical equation of state of the type pv = A + B/v + C/v2 + D/v4 + E/v6 + F/v8, where the coefficients A ... F, called by him virial coefficients, are determined as functions of the temperature to fit the observations. Now it is possible by various methods to obtain a theoretical expression for B as a function of the temperature and a strict comparison can then be made between theory and experiment. Unfortunately the solution for B, although applicable to any molecular model of spherical symmetry, is purely formal and contains an integral which can be evaluated only in special cases. This has been done up to now for only two simple models, viz., a van der Waals molecule, and a molecule repelling according to an inverse power law (without attraction), but it is shown in this paper that it can also be evaluated in the case of the model, which was successful in explaining viscosity results. As the two other models just mentioned are particular cases of this, the appropriate formulæ for B are easily deduced from the general one given here.

This paper examines the robustness of explanatory variables in cross-country economic growth regressions. It introduces and employs a novel approach, Bayesian Averaging of Classical Estimates (BACE), which constructs estimates by averaging OLS coefficients across models. The weights given to individual regressions have a Bayesian justification similar to the Schwarz model selection criterion. Of 67 explanatory variables we find 18 to be significantly and robustly partially correlated with long-term growth and another three variables to be marginally related. The strongest evidence is for the relative price of investment, primary school enrollment, and the initial level of real GDP per capita.

BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

Codon usage data has been compiled for 110 yeast genes. Cluster analysis on relative synonymous codon usage revealed two distinct groups of genes. One group corresponds to highly expressed genes, and has much more extreme synonymous codon preference. The pattern of codon usage observed is consistent with that expected if a need to match abundant tRNAs, and intermediacy of tRNA-mRNA interaction energies are important selective constraints. Thus codon usage in the highly expressed group shows a higher correlation with tRNA abundance, a greater degree of third base pyrimidine bias, and a lesser tendency to the A+T richness which is characteristic of the yeast genome. The cluster analysis can be used to predict the likely level of gene expression of any gene, and identifies the pattern of codon usage likely to yield optimal gene expression in yeast.

Pre-eclampsia is a common disorder that particularly affects first pregnancies. The clinical presentation is highly variable but hypertension and proteinuria are usually seen. These systemic signs arise from soluble factors released from the placenta as a result of a response to stress of syncytiotrophoblast. There are two sub-types: early and late onset pre-eclampsia, with others almost certainly yet to be identified. Early onset pre-eclampsia arises owing to defective placentation, whilst late onset pre-eclampsia may center around interactions between normal senescence of the placenta and a maternal genetic predisposition to cardiovascular and metabolic disease. The causes, placental and maternal, vary among individuals. Recent research has focused on placental-uterine interactions in early pregnancy. The aim now is to translate these findings into new ways to predict, prevent, and treat pre-eclampsia.

Abstract The second-generation of gravitational-wave detectors are just starting operation, and have already yielding their first detections. Research is now concentrated on how to maximize the scientific potential of gravitational-wave astronomy. To support this effort, we present here design targets for a new generation of detectors, which will be capable of observing compact binary sources with high signal-to-noise ratio throughout the Universe.

Mutations in the filaggrin gene are associated with a broad range of skin and allergic diseases. The biology of this molecule and the role of mutations in its altered function offer new insights into a range of conditions not previously thought to be related to one another.

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

How humans solve the cocktail party problem remains unknown. However, progress has been made recently thanks to the realization that cortical activity tracks the amplitude envelope of speech. This has led to the development of regression methods for studying the neurophysiology of continuous speech. One such method, known as stimulus-reconstruction, has been successfully utilized with cortical surface recordings and magnetoencephalography (MEG). However, the former is invasive and gives a relatively restricted view of processing along the auditory hierarchy, whereas the latter is expensive and rare. Thus it would be extremely useful for research in many populations if stimulus-reconstruction was effective using electroencephalography (EEG), a widely available and inexpensive technology. Here we show that single-trial (≈60 s) unaveraged EEG data can be decoded to determine attentional selection in a naturalistic multispeaker environment. Furthermore, we show a significant correlation between our EEG-based measure of attention and performance on a high-level attention task. In addition, by attempting to decode attention at individual latencies, we identify neural processing at ∼200 ms as being critical for solving the cocktail party problem. These findings open up new avenues for studying the ongoing dynamics of cognition using EEG and for developing effective and natural brain-computer interfaces.

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Broadening of the Debye-Scherrer lines in x-ray photographs of cold-worked metals has been attributed (i) to breaking up of the crystals into " crystallites " whose linear dimensions are less, similar10 -5 cm., (ii) to the presence of crystal grains of different lattice parameters, and (iii) to distortion of comparatively large crystal grains. The broadening to be expected on the last hypothesis is worked out approximately. It is found that the " apparent strain " is given by ηidentical withβ cot Θ=2/Φ hkl (0), where β is the (corrected) integral breadth of the hkl reflection, Θ is the Bragg angle, and Φ hhl ( e ) de is the fraction of the crystal for which the tensile strain in the hkl direction is between e and e + de. To relate η with the internal stresses requires some approximations. In cubic crystals fairly plausible assumptions lead to the equation η 2 = A + BH , where A and B are constants involving the elastic moduli and the mean square values of the direct and shear stresses, and H identical with( k 2 l 2 + l 2 h 2 + h 2 k 2 )/( h 2 + k 2 + l 2 ) 2 . This equation is verified within the rather large experimental error for metal filings and wire. Details of the experimental work will be published elsewhere.

Abstract Until our knowledge of the disposition and motion of the electrons in atoms and molecules is more complete, we cannot hope to make a direct calculation of the nature of the forces called into play during an encounter between molecules in a gas. It is true that a step in this direction has recently been made by Debye, who has investigated the nature of the field in the neighbourood of a hydrogen atom, assumed to consist of a negative charge in motion in circular orbit about a positive nucleus, and has shown how the pulsating eld gives rise on the whole to a force of repulsion, as well as one of attraction n a unit negative charge. But it is difficult to see how this work can be extended to more complex systems. At present we can only hope to derive information by more indirect methods. One such method is to assume a definite law of force, and then by the methods of the kinetic theory to deduce the appropriate law of dependence of the viscosity of a gas on temperature. Comparison with the actual law, as observed experimentally, serves to support or discredit the assumed law of molecular interaction. Unfortunately, the calculations involved in the application of be kinetic theory are so complicated that progress has been made only in certain simple cases. Thus, the original investigation by Maxwell applied only to molecules repelling as the inverse fifth power law. His work has since be generalised by Chapman and Enskog and formulæ have been obtained: the coefficient of viscosity in the case of (i) molecules, which repel according an inverse nth power law, (ii) molecules which behave on collision like rig elastic spheres and (iii) molecules which behave as rigid elastic spheres with weak attractive field of force surrounding them. Of these models the la generally referred to as Sutherland’s model, is found to give the best agreement between theory and experiment. But the agreement is by no means perfe As Schmidt, Bestelmeyer, Vogel, and others have pointed out, there considerable divergence from observed values a t low temperatures.

Understanding how brains process sensory signals in natural environments is one of the key goals of twenty-first century neuroscience. While brain imaging and invasive electrophysiology will play key roles in this endeavor, there is also an important role to be played by noninvasive, macroscopic techniques with high temporal resolution such as electro- and magnetoencephalography. But challenges exist in determining how best to analyze such complex, time-varying neural responses to complex, time-varying and multivariate natural sensory stimuli. There has been a long history of applying system identification techniques to relate the firing activity of neurons to complex sensory stimuli and such techniques are now seeing increased application to EEG and MEG data. One particular example involves fitting a filter-often referred to as a temporal response function-that describes a mapping between some feature(s) of a sensory stimulus and the neural response. Here, we first briefly review the history of these system identification approaches and describe a specific technique for deriving temporal response functions known as regularized linear regression. We then introduce a new open-source toolbox for performing this analysis. We describe how it can be used to derive (multivariate) temporal response functions describing a mapping between stimulus and response in both directions. We also explain the importance of regularizing the analysis and how this regularization can be optimized for a particular dataset. We then outline specifically how the toolbox implements these analyses and provide several examples of the types of results that the toolbox can produce. Finally, we consider some of the limitations of the toolbox and opportunities for future development and application.

It is well accepted that CNS inflammation has a role in the progression of chronic neurodegenerative disease, although the mechanisms through which this occurs are still unclear. The inflammatory response during most chronic neurodegenerative disease is dominated by the microglia and mechanisms by which these cells contribute to neuronal damage and degeneration are the subject of intense study. More recently it has emerged that systemic inflammation has a significant role to play in the progression of these diseases. Well-described adaptive pathways exist to transduce systemic inflammatory signals to the brain, but activation of these pathways appears to be deleterious to the brain if the acute insult is sufficiently robust, as in severe sepsis, or sufficiently prolonged, as in repeated stimulation with robust doses of inflammogens such as lipopolysaccharide (LPS). Significantly, moderate doses of inflammogens produce new pathology in the brain and exacerbate or accelerate features of disease when superimposed upon existing pathology or in the context of genetic predisposition. It is now apparent in multiple chronic disease states, and in ageing, that microglia are primed by prior pathology, or by genetic predisposition, to respond more vigorously to subsequent inflammatory stimulation, thus transforming an adaptive CNS inflammatory response to systemic inflammation, into one that has deleterious consequences for the individual. In this review, the preclinical and clinical evidence supporting a significant role for systemic inflammation in chronic neurodegenerative diseases will be discussed. Mechanisms by which microglia might effect neuronal damage and dysfunction, as a consequence of systemic stimulation, will be highlighted.

Nobel Lecture

Abstract 1. The object of the present paper can be best explained by referring to a sentence which occurs in a paper by Professor G. H. Darwin. This is as follows:— “The principal question involved in the nebular hypothesis seems to be the stability of a rotating mass of gas; but, unfortunately, this has remained up to now an untouched field of mathematical research. We can only judge of probable results from the investigations which have been made concerning the stability of a rotating mass of liquid.”

Obesity is an established risk factor for chronic disease and premature death, but losing weight and keeping it off is difficult. Therefore, although obese individuals may know that they are at higher risk of disease and early death, they still may not be able to lose weight and maintain weight loss. Perhaps health professionals should focus less on weight and more on how to enhance and maintain health for people of all sizes and shapes.

BACKGROUND: Chronic neurodegeneration results in microglial activation, but the contribution of inflammation to the progress of neurodegeneration remains unclear. We have shown that microglia express low levels of proinflammatory cytokines during chronic neurodegeneration but are "primed" to produce a more proinflammatory profile after systemic challenge with bacterial endotoxin (lipopolysaccharide [LPS]). METHODS: Here, we investigated whether intraperitoneal (IP) challenge with LPS, to mimic systemic infection, in the early stages of prion disease can 1) produce exaggerated acute behavioral (n = 9) and central nervous system (CNS) inflammatory (n = 4) responses in diseased animals compared with control animals, and 2) whether a single LPS challenge can accelerate disease progression (n = 34-35). RESULTS: Injection of LPS (100 microg/kg), at 12 weeks postinoculation (PI), resulted in heightened CNS interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-beta (IFN-beta) transcription and microglial IL-1beta translation in prion-diseased animals relative to control animals. This inflammation caused exaggerated impairments in burrowing and locomotor activity, and induced hypothermia and cognitive changes in prion-diseased animals that were absent in LPS-treated control animals. At 15 weeks PI, LPS (500 microg/kg) acutely impaired motor coordination and muscle strength in prion-diseased but not in control animals. After recovery, these animals also showed earlier onset of disease-associated impairments on these parameters. CONCLUSIONS: These data demonstrate that transient systemic inflammation superimposed on neurodegenerative disease acutely exacerbates cognitive and motor symptoms of disease and accelerates disease progression. These deleterious effects of systemic inflammation have implications for the treatment of chronic neurodegeneration and associated delirium.