468 research outputs found
Intravenous immunoglobulin in the treatment of primary trigeminal neuralgia refractory to carbamazepine: a study protocol[ISRCTN33042138]
BACKGROUND: We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin (IVIG) in a prospective, open-label cohort study. A randomised, placebo controlled, double blinded study is needed to confirm these results. We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia (rpTN), as these had responded particularly well to IVIG. A protocol involving the use of IVIG in rpTN is complex for three reasons: 1. The effect of IVIG does not follow simple dose-response rules; 2. The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and >1 year; 3. TN is characterized by extremely severe pain, for which operative intervention is (if temporarily) helpful in most patients. DESIGN: A placebo controlled, parallel, add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study. Study groups are compared using Kaplan-Maier survival analysis. Patients record their response to treatment ("severe, moderate, slight, no pain"). The study coordinator monitors pain diaries. Severe or moderate pain of three days duration will result in termination of the study for that patient. CONCLUSIONS: This study design utilizes a method of survival analysis and is novel in chronic pain research. It allows for both early departure from the study and voluntary crossover upon non-response. It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes
Dual Identities inside the Gluon and the Graviton Scattering Amplitudes
Recently, Bern, Carrasco and Johansson conjectured dual identities inside the
gluon tree scattering amplitudes. In this paper, we use the properties of the
heterotic string and open string tree scattering amplitudes to refine and
derive these dual identities. These identities can be carried over to loop
amplitudes using the unitarity method. Furthermore, given the -gluon (as
well as gluon-gluino) tree amplitudes, -graviton (as well as
graviton-gravitino) tree scattering amplitudes can be written down immediately,
avoiding the derivation of Feynman rules and the evaluation of Feynman diagrams
for graviton scattering amplitudes.Comment: 43 pages, 3 figures; typos corrected, a few points clarified
The Kinematic Algebra From the Self-Dual Sector
We identify a diffeomorphism Lie algebra in the self-dual sector of
Yang-Mills theory, and show that it determines the kinematic numerators of
tree-level MHV amplitudes in the full theory. These amplitudes can be computed
off-shell from Feynman diagrams with only cubic vertices, which are dressed
with the structure constants of both the Yang-Mills colour algebra and the
diffeomorphism algebra. Therefore, the latter algebra is the dual of the colour
algebra, in the sense suggested by the work of Bern, Carrasco and Johansson. We
further study perturbative gravity, both in the self-dual and in the MHV
sectors, finding that the kinematic numerators of the theory are the BCJ
squares of the Yang-Mills numerators.Comment: 29 pages, 5 figures. v2: references added, published versio
CHY representations for gauge theory and gravity amplitudes with up to three massive particles
We show that a wide class of tree-level scattering amplitudes involving
scalars, gauge bosons, and gravitons, up to three of which may be massive, can
be expressed in terms of a Cachazo-He-Yuan representation as a sum over
solutions of the scattering equations. These amplitudes, when expressed in
terms of the appropriate kinematic invariants, are independent of the masses
and therefore identical to the corresponding massless amplitudes.Comment: 20 pages, 1 figure; v2: minor typos corrected, published versio
Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise
We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention
Hypoxia Alters Cell Cycle Regulatory Protein Expression and Induces Premature Maturation of Oligodendrocyte Precursor Cells
Periventricular white matter injury (PWMI) is a common form of brain injury sustained by preterm infants. A major factor that predisposes to PWMI is hypoxia. Because oligodendrocytes (OLs) are responsible for myelination of axons, abnormal OL development or function may affect brain myelination. At present our understanding of the influences of hypoxia on OL development is limited. To examine isolated effects of hypoxia on OLs, we examined the influences of hypoxia on OL development in vitro.Cultures of oligodendrocyte precursor cells (OPCs) were prepared from mixed glial cultures and were 99% pure. OPCs were maintained at 21% O(2) or hypoxia (1% or 4% O(2)) for up to 7 days. We observed that 1% O(2) lead to an increase in the proportion of myelin basic protein (MBP)-positive OLs after 1 week in culture, and a decrease in the proportion of platelet-derived growth factor receptor alpha (PDGFRalpha)-positive cells suggesting premature OL maturation. Increased expression of the cell cycle regulatory proteins p27(Kip1) and phospho-cdc2, which play a role in OL differentiation, was seen as well.These results show that hypoxia interferes with the normal process of OL differentiation by inducing premature OPC maturation
Archaeological Support for the Three-Stage Expansion of Modern Humans across Northeastern Eurasia and into the Americas
Background
Understanding the dynamics of the human range expansion across northeastern Eurasia during the late Pleistocene is central to establishing empirical temporal constraints on the colonization of the Americas [1]. Opinions vary widely on how and when the Americas were colonized, with advocates supporting either a pre-[2] or post-[1], [3], [4], [5], [6] last glacial maximum (LGM) colonization, via either a land bridge across Beringia [3], [4], [5], a sea-faring Pacific Rim coastal route [1], [3], a trans-Arctic route [4], or a trans-Atlantic oceanic route [5]. Here we analyze a large sample of radiocarbon dates from the northeast Eurasian Upper Paleolithic to identify the origin of this expansion, and estimate the velocity of colonization wave as it moved across northern Eurasia and into the Americas.
Methodology/Principal Findings
We use diffusion models [6], [7] to quantify these dynamics. Our results show the expansion originated in the Altai region of southern Siberia ~46kBP , and from there expanded across northern Eurasia at an average velocity of 0.16 km per year. However, the movement of the colonizing wave was not continuous but underwent three distinct phases: 1) an initial expansion from 47-32k calBP; 2) a hiatus from ~32-16k calBP, and 3) a second expansion after the LGM ~16k calBP. These results provide archaeological support for the recently proposed three-stage model of the colonization of the Americas [8], [9]. Our results falsify the hypothesis of a pre-LGM terrestrial colonization of the Americas and we discuss the importance of these empirical results in the light of alternative models.
Conclusions/Significance
Our results demonstrate that the radiocarbon record of Upper Paleolithic northeastern Eurasia supports a post-LGM terrestrial colonization of the Americas falsifying the proposed pre-LGM terrestrial colonization of the Americas. We show that this expansion was not a simple process, but proceeded in three phases, consistent with genetic data, largely in response to the variable climatic conditions of late Pleistocene northeast Eurasia. Further, the constraints imposed by the spatiotemporal gradient in the empirical radiocarbon record across this entire region suggests that North America cannot have been colonized much before the existing Clovis radiocarbon record suggests
Do Children Who Move Home and School Frequently Have Poorer Educational Outcomes in Their Early Years at School? An Anonymised Cohort Study
Frequent mobility has been linked to poorer educational attainment. We investigated the association between moving
home and moving school frequently and the early childhood formal educational achievement. We carried out a cohort
analysis of 121,422 children with anonymised linked records. Our exposure measures were: 1) the number of residential
moves registered with a health care provider, and 2) number of school moves. Our outcome was the formal educational
assessment at age 6–7. Binary regression modeling was used to examine residential moves within the three time periods: 0
– ,1 year; 1 – ,4 years and 4 – ,6 years. School moves were examined from age 4 to age 6. We adjusted for demographics,
residential moves at different times, school moves and birth related variables. Children who moved home frequently were
more likely not to achieve in formal assessments compared with children not moving. Adjusted odds ratios were significant
for 3 or more moves within the time period 1 –,4 years and for any number of residential moves within the time period 4–
,6 years. There was a dose response relationship, with increased odds ratios with increased frequency of residential moves
(2 or more moves at 4–,6 years, adjusted odds ratio 1.16 (1.03, 1.29). The most marked effect was seen with frequent
school moves where 2 or more moves resulted in an adjusted odds ratio of 2.33 (1.82, 2.98). This is the first study to examine
the relationship between residential and school moves in early childhood and the effect on educational attainment.
Children experiencing frequent mobility may be disadvantaged and should be closely monitored. Additional educational
support services should be afforded to children, particularly those who frequently change school, in order to help them
achieve the expected educational standards
Updated Three-Stage Model for the Peopling of the Americas
Background: We re-assess support for our three stage model for the peopling of the Americas in light of a recent report that identified nine non-Native American mitochondrial genome sequences that should not have been included in our initial analysis. Removal of these sequences results in the elimination of an early (i.e.,40,000 years ago) expansion signal we had proposed for the proto-Amerind population. Methodology/Findings: Bayesian skyline plot analysis of a new dataset of Native American mitochondrial coding genomes confirms the absence of an early expansion signal for the proto-Amerind population and allows us to reduce the variation around our estimate of the New World founder population size. In addition, genetic variants that define New World founder haplogroups are used to estimate the amount of time required between divergence of proto-Amerinds from the Asian gene pool and expansion into the New World. Conclusions/Significance: The period of population isolation required for the generation of New World mitochondrial founder haplogroup-defining genetic variants makes the existence of three stages of colonization a logical conclusion. Thus, our three stage model remains an important and useful working hypothesis for researchers interested in the peopling of th
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