Author response: Effects of orthostatic hypotension on cognition in Parkinson disease

OBJECTIVE: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in persons with Parkinson's disease (PD) without dementia. METHODS: There were 55 participants: 37 non-demented individuals with idiopathic PD, including 18 with OH (PDOH), and 19 without (PDWOH), and18 control participants (C). All participants completed neuropsychological tests in the supine and in the upright tilted position. Blood pressure was assessed in each posture using a standardized oscillometric cuff at the right brachial artery. RESULTS: The two PD groups performed similarly while supine, with a profile notable for executive dysfunction consisting of deficits in sustained attention, response inhibition, and semantic verbal fluency, as well as reduced verbal memory encoding and retention. When upright, these deficits were exacerbated and broadened to include additional cognitive functions in the PDOH group: deficits in phonemic verbal fluency, psychomotor speed, and both basic and complex aspects of auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, though the PDOH group had a wider range of deficits in the executive functioning and memory domains and was the only group to show significant changes in visuospatial skills. CONCLUSIONS: Cognitive deficits in idiopathic PD have been widely reported, though assessments are typically performed in the supine position. While both PD groups had supine deficits that aligned with prior studies and clinical findings, we demonstrated that those with PD and orthostatic hypotension had transient, posture-mediated changes in excess of those found in PD without autonomic failure. These observed changes suggest an acute, reversible effect, and as orthostatic hypotension is a significant comorbid factor in PD, an independent target for clinical intervention. Further understanding of the effects of autonomic failure on cognition in other disorders is desirable, particularly in the context of neuroimaging studies and clinical assessments where data are collected only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with autonomic failure also has implications for functional activities of daily living and overall quality of life.Accepted manuscrip

Effects of orthostatic hypotension on cognition in Parkinson's disease

OBJECTIVE: To investigate the relation between orthostatic hypotension (OH) and posture-mediated cognitive impairment in Parkinson disease (PD) using a cross-sectional and within-group design. METHODS: Individuals without dementia with idiopathic PD included 18 with OH (PDOH) and 19 without OH; 18 control participants were also included. Neuropsychological tests were conducted in supine and upright-tilted positions. Blood pressure was assessed in each posture. RESULTS: The PD groups performed similarly while supine, demonstrating executive dysfunction in sustained attention and response inhibition, and reduced semantic fluency and verbal memory (encoding and retention). Upright posture exacerbated and broadened these deficits in the PDOH group to include phonemic fluency, psychomotor speed, and auditory working memory. When group-specific supine scores were used as baseline anchors, both PD groups showed cognitive changes following tilt, with the PDOH group exhibiting a wider range of deficits in executive function and memory as well as significant changes in visuospatial function. CONCLUSIONS: Cognitive deficits in PD have been widely reported with assessments performed in the supine position, as seen in both our PD groups. Here we demonstrated that those with PDOH had transient, posture-mediated changes in excess of those found in PD without OH. These observed changes suggest an acute, reversible effect. Understanding the effects of OH due to autonomic failure on cognition is desirable, particularly as neuroimaging and clinical assessments collect data only in the supine or seated positions. Identification of a distinct neuropsychological profile in PD with OH has quality of life implications, and OH presents itself as a possible target for intervention in cognitive disturbance.Accepted manuscriptAccepted manuscrip

Punctuated chromatin states regulate Plasmodium falciparum antigenic variation at the intron and 2 kb upstream regions

2 kb upstream region FAIRE-Seq signal comparison between var genes and different gene families (P-value is calculated based on Wilcoxon-Rank-Sum test, FDR indicates false discovery rate). (XLSX 53 kb

Entropy in the RST Model

The RST Model is given boundary term and Z-field so that it is well-posed and local. The Euclidean method is described for general theory and used to calculate the RST intrinsic entropy. The evolution of this entropy for the shockwave solutions is found and obeys a second law.Comment: 10 pages, minor revisions, published version in Late

Bubbling AdS Black Holes

We explore the non-BPS analog of `AdS bubbles', which are regular spherically symmetric 1/2 BPS geometries in type IIB supergravity. They have regular horizons and can be thought of as bubbling generalizations of non-extremal AdS black hole solutions in five-dimensional gauged supergravity. Due to the appearance of the Heun equation even at the linearized level, various approximation and numerical methods are needed in order to extract information about this system. We study how the vacuum expectation value and mass of a particular dimension two chiral primary operator depend on the temperature and chemical potential of the thermal Yang-Mills theory. In addition, the mass of the bubbling AdS black holes is computed. As is shown numerically, there are also non-BPS solitonic bubbles which are completely regular and arise from continuous deformations of BPS AdS bubbles.Comment: 37 pages, 2 figure

New supersymmetric solutions of N=2, D=5 gauged supergravity with hyperscalars

We construct new supersymmetric solutions, including AdS bubbles, in an N=2 truncation of five-dimensional N=8 gauged supergravity. This particular truncation is given by N=2 gauged supergravity coupled to two vector multiples and three incomplete hypermultiplets, and was originally investigated in the context of obtaining regular AdS bubble geometries with multiple active R-charges. We focus on cohomogeneity-one solutions corresponding to objects with two equal angular momenta and up to three independent R-charges. Curiously, we find a new set of zero and negative mass solitons asymptotic to AdS_5/Z_k, for k \ge 3, which are everywhere regular without closed timelike curves.Comment: Latex 3 times, 42 page

Plane waves with weak singularities

We study a class of time dependent solutions of the vacuum Einstein equations which are plane waves with weak null singularities. This singularity is weak in the sense that though the tidal forces diverge at the singularity, the rate of divergence is such that the distortion suffered by a freely falling observer remains finite. Among such weak singular plane waves there is a sub-class which do not exhibit large back reaction in the presence of test scalar probes. String propagation in these backgrounds is smooth and there is a natural way to continue the metric beyond the singularity. This continued metric admits string propagation without the string becoming infinitely excited. We construct a one parameter family of smooth metrics which are at a finite distance in the space of metrics from the extended metric and a well defined operator in the string sigma model which resolves the singularity.Comment: 22 pages, Added references and clarifying comment

Heat kernel regularization of the effective action for stochastic reaction-diffusion equations

The presence of fluctuations and non-linear interactions can lead to scale dependence in the parameters appearing in stochastic differential equations. Stochastic dynamics can be formulated in terms of functional integrals. In this paper we apply the heat kernel method to study the short distance renormalizability of a stochastic (polynomial) reaction-diffusion equation with real additive noise. We calculate the one-loop {\emph{effective action}} and its ultraviolet scale dependent divergences. We show that for white noise a polynomial reaction-diffusion equation is one-loop {\emph{finite}} in $d=0$ and $d=1$, and is one-loop renormalizable in $d=2$ and $d=3$ space dimensions. We obtain the one-loop renormalization group equations and find they run with scale only in $d=2$.Comment: 21 pages, uses ReV-TeX 3.

The Heat Kernel on AdS_3 and its Applications

We derive the heat kernel for arbitrary tensor fields on S^3 and (Euclidean) AdS_3 using a group theoretic approach. We use these results to also obtain the heat kernel on certain quotients of these spaces. In particular, we give a simple, explicit expression for the one loop determinant for a field of arbitrary spin s in thermal AdS_3. We apply this to the calculation of the one loop partition function of N=1 supergravity on AdS_3. We find that the answer factorizes into left- and right-moving super Virasoro characters built on the SL(2, C) invariant vacuum, as argued by Maloney and Witten on general grounds.Comment: 46 pages, LaTeX, v2: Reference adde

The impact of the demographic transition on dengue in Thailand: Insights from a statistical analysis and mathematical modeling

Background: An increase in the average age of dengue hemorrhagic fever (DHF) cases has been reported in Thailand. The cause of this increase is not known. Possible explanations include a reduction in transmission due to declining mosquito populations, declining contact between human and mosquito, and changes in reporting. We propose that a demographic shift toward lower birth and death rates has reduced dengue transmission and lengthened the interval between large epidemics. Methods and Findings: Using data from each of the 72 provinces of Thailand, we looked for associations between force of infection (a measure of hazard, defined as the rate per capita at which susceptible individuals become infected) and demographic and climactic variables. We estimated the force of infection from the age distribution of cases from 1985 to 2005. We find that the force of infection has declined by 2% each year since a peak in the late 1970s and early 1980s. Contrary to recent findings suggesting that the incidence of DHF has increased in Thailand, we find a small but statistically significant decline in DHF incidence since 1985 in a majority of provinces. The strongest predictor of the change in force of infection and the mean force of infection is the median age of the population. Using mathematical simulations of dengue transmission we show that a reduced birth rate and a shift in the population's age structure can explain the shift in the age distribution of cases, reduction of the force of infection, and increase in the periodicity of multiannual oscillations of DHF incidence in the absence of other changes. Conclusions: Lower birth and death rates decrease the flow of susceptible individuals into the population and increase the longevity of immune individuals. The increase in the proportion of the population that is immune increases the likelihood that an infectious mosquito will feed on an immune individual, reducing the force of infection. Though the force of infection has decreased by half, we find that the critical vaccination fraction has not changed significantly, declining from an average of 85% to 80%. Clinical guidelines should consider the impact of continued increases in the age of dengue cases in Thailand. Countries in the region lagging behind Thailand in the demographic transition may experience the same increase as their population ages. The impact of demographic changes on the force of infection has been hypothesized for other diseases, but, to our knowledge, this is the first observation of this phenomenon