Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes

BACKGROUND: The autism spectrum encompasses a set of complex multigenic developmental disorders that severely impact the development of language, non-verbal communication, and social skills, and are associated with odd, stereotyped, repetitive behavior and restricted interests. To date, diagnosis of these neurologically based disorders relies predominantly upon behavioral observations often prompted by delayed speech or aberrant behavior, and there are no known genes that can serve as definitive biomarkers for the disorders. RESULTS: Here we demonstrate, for the first time, that lymphoblastoid cell lines from monozygotic twins discordant with respect to severity of autism and/or language impairment exhibit differential gene expression patterns on DNA microarrays. Furthermore, we show that genes important to the development, structure, and/or function of the nervous system are among the most differentially expressed genes, and that many of these genes map closely in silico to chromosomal regions containing previously reported autism candidate genes or quantitative trait loci. CONCLUSION: Our results provide evidence that novel candidate genes for autism may be differentially expressed in lymphoid cell lines from individuals with autism spectrum disorders. This finding further suggests the possibility of developing a molecular screen for autism based on expressed biomarkers in peripheral blood lymphocytes, an easily accessible tissue. In addition, gene networks are identified that may play a role in the pathophysiology of autism

Southern Ocean Overturning Compensation in an Eddy-Resolving Climate Simulation

The Southern Ocean’s Antarctic Circumpolar Current (ACC) and meridional overturning circulation (MOC) response to increasing zonal wind stress is, for the first time, analyzed in a high-resolution (0.1° ocean and 0.25° atmosphere), fully coupled global climate simulation using the Community Earth System Model. Results from a 20-yr wind perturbation experiment, where the Southern Hemisphere zonal wind stress is increased by 50% south of 30°S, show only marginal changes in the mean ACC transport through Drake Passage—an increase of 6% [136–144 Sverdrups (Sv; 1 Sv ≡ 10^6 m^3 s^(−1))] in the perturbation experiment compared with the control. However, the upper and lower circulation cells of the MOC do change. The lower cell is more affected than the upper cell with a maximum increase of 64% versus 39%, respectively. Changes in the MOC are directly linked to changes in water mass transformation from shifting surface isopycnals and sea ice melt, giving rise to changes in surface buoyancy forcing. The increase in transport of the lower cell leads to upwelling of warm and salty Circumpolar Deep Water and subsequent melting of sea ice surrounding Antarctica. The MOC is commonly supposed to be the sum of two opposing components: a wind- and transient-eddy overturning cell. Here, the transient-eddy overturning is virtually unchanged and consistent with a large-scale cancellation of localized regions of both enhancement and suppression of eddy kinetic energy along the mean path of the ACC. However, decomposing the time-mean overturning into a time- and zonal-mean component and a standing-eddy component reveals partial compensation between wind-driven and standing-eddy components of the circulation

Response of the North Atlantic thermohaline circulation and ventilation to increasing carbon dioxide in CCSM3

Author Posting. © American Meteorological Society 2006. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 19 (2006): 2382–2397, doi:10.1175/JCLI3757.1.The response of the North Atlantic thermohaline circulation to idealized climate forcing of 1% per year compound increase in CO2 is examined in three configurations of the Community Climate System Model version 3 that differ in their component model resolutions. The strength of the Atlantic overturning circulation declines at a rate of 22%–26% of the corresponding control experiment maximum overturning per century in response to the increase in CO2. The mean meridional overturning and its variability on decadal time scales in the control experiments, the rate of decrease in the transient forcing experiments, and the rate of recovery in periods of CO2 stabilization all increase with increasing component model resolution. By examining the changes in ocean surface forcing with increasing CO2 in the framework of the water-mass transformation function, we show that the decline in the overturning is driven by decreasing density of the subpolar North Atlantic due to increasing surface heat fluxes. While there is an intensification of the hydrologic cycle in response to increasing CO2, the net effect of changes in surface freshwater fluxes on those density classes that are involved in deep-water formation is to increase their density; that is, changes in surface freshwater fluxes act to maintain a stronger overturning circulation. The differences in the control experiment overturning strength and the response to increasing CO2 are well predicted by the corresponding differences in the water-mass transformation rate. Reduction of meridional heat transport and enhancement of meridional salt transport from mid- to high latitudes with increasing CO2 also act to strengthen the overturning circulation. Analysis of the trends in an ideal age tracer provides a direct measure of changes in ocean ventilation time scale in response to increasing CO2. In the subpolar North Atlantic south of the Greenland–Scotland ridge system, there is a significant increase in subsurface ages as open-ocean deep convection is diminished and ventilation switches to a predominance of overflow waters. In middle and low latitudes there is a decrease in age within and just below the thermocline in response to a decrease in the upwelling of old deep waters. However, when considering ventilation within isopycnal layers, age increases for layers in and below the thermocline due to the deepening of isopycnals in response to global warming

Impact of operative indication and surgical complexity on outcomes after thoracic endovascular aortic repair at National Surgical Quality Improvement Program Centers

IntroductionThoracic endovascular aortic repair (TEVAR) devices are increasingly being utilized to treat aortic pathologies outside of the original Food & Drug Administration (FDA) approval for nonruptured descending thoracic aorta aneurysms (DTAs). The objective of this study was to evaluate the outcomes of patients undergoing TEVAR, elucidating the role of surgical and pathologic variables on morbidity and mortality.MethodsNational Surgical Quality Improvement Program (NSQIP) data were reviewed for all patients undergoing endovascular thoracic aorta repair from 2005 to 2007. The patients' operative indication and surgical complexity were used to divide them into study and control populations. Comorbid profiles were assessed utilizing a modified Charlson Comorbidity Index (CCI). Thirty-day occurrences of mortality and serious adverse events (SAEs) were used as study endpoints. Univariate and multivariate models were created using demographic and clinical variables to assess for significant differences in endpoints (P ≤ .05).ResultsA total of 440 patients undergoing TEVAR were identified. When evaluating patients based on operative indication, the ruptured population had increased mortality and SAE rates compared to the nonruptured DTA population (22.6% vs 6.2%;P < .01 and 35.5% vs 9.1%;P < .01, respectively). Further analysis by surgical complexity revealed increased mortality and SAE rates when comparing the brachiocephalic aortic debranching population to the noncovered left subclavian artery population (23.1% vs 6.5%; P = .02 and 30.8% vs 9.1%; P < .01, respectively). Multivariate analysis demonstrated that operative indication was not a correlate of mortality or SAEs (odds ratio [OR], 0.95; P = .92 and OR, 1.42; P = .39, respectively); however, brachiocephalic aortic debranching exhibited a deleterious effect on mortality (OR, 8.75; P < .01) and SAE rate (OR, 6.67; P = .01).ConclusionThe operative indication for a TEVAR procedure was not found to be a predictor of poor patient outcome. Surgical complexity, specifically the need for brachiocephalic aortic debranching and aortoiliac conduit, was shown to influence the occurrence of SAEs in a multivariate model. Comparative data, such as these, illustrate real-world outcomes of patients undergoing TEVAR outside of the original FDA-approved indications. This information is of paramount importance to various stakeholders, including third-party payers, the device industry, regulatory agencies, surgeons, and their patients

Effect of Carbon Dioxide on the Twinkling Artifact in Ultrasound Imaging of Kidney Stones: A Pilot Study

Bone demineralization, dehydration and stasis put astronauts at increased risk of forming kidney stones in space. The color-Doppler ultrasound "twinkling artifact," which highlights kidney stones with color, can make stones readily detectable with ultrasound; however, our previous results suggest twinkling is caused by microbubbles on the stone surface which could be affected by the elevated levels of carbon dioxide found on space vehicles. Four pigs were implanted with kidney stones and imaged with ultrasound while the anesthetic carrier gas oscillated between oxygen and air containing 0.8% carbon dioxide. On exposure of the pigs to 0.8% carbon dioxide, twinkling was significantly reduced after 9-25 min and recovered when the carrier gas returned to oxygen. These trends repeated when pigs were again exposed to 0.8% carbon dioxide followed by oxygen. The reduction of twinkling caused by exposure to elevated carbon dioxide may make kidney stone detection with twinkling difficult in current space vehicles

Hyperkalemia and electrocardiogram manifestations in end-stage renal disease

Hyperkalemia is one of the more common acute life-threatening metabolic emergencies. The aim of our study is to determine the correlation and accuracy of abnormal ECG parameters as a function of serum potassium concentration in the end-stage renal disease (ESRD) population. We performed a retrospective chart review of emergency department patients presenting with ESRD and receiving emergent hemodialysis treatment. A total of 96 patients, each with five independent ED visits, provided 480 sets of ECGs and electrolytes. Of these, four ECGs were excluded for inability to interpret, leaving a total of 476 patient encounters that met all inclusion criteria. Linear regression analysis on the limited data set for serum potassium versus T/R in V2, V3, and V4, PR, and QRS found weak correlations (

The MeerKAT Fornax Survey

We present the science case and observations plan of the MeerKAT Fornax Survey, an HI and radio continuum survey of the Fornax galaxy cluster to be carried out with the SKA precursor MeerKAT. Fornax is the second most massive cluster within 20 Mpc and the largest nearby cluster in the southern hemisphere. Its low X-ray luminosity makes it representative of the environment where most galaxies live and where substantial galaxy evolution takes place. Fornax's ongoing growth makes it an excellent laboratory for studying the assembly of clusters, the physics of gas accretion and stripping in galaxies falling in the cluster, and the connection between these processes and the neutral medium in the cosmic web. We will observe a region of 12 deg$^2$ reaching a projected distance of 1.5 Mpc from the cluster centre. This will cover a wide range of environment density out to the outskirts of the cluster, where gas-rich in-falling groups are found. We will: study the HI morphology of resolved galaxies down to a column density of a few times 1e+19 cm$^{-2}$ at a resolution of 1 kpc; measure the slope of the HI mass function down to M(HI) 5e+5 M(sun); and attempt to detect HI in the cosmic web reaching a column density of 1e+18 cm$^{-2}$ at a resolution of 10 kpc.Comment: Proceedings of Science, "MeerKAT Science: On the Pathway to the SKA", Stellenbosch, 25-27 May 201

Constraints on the relationship between stellar mass and halo mass at low and high redshift

We use a statistical approach to determine the relationship between the stellar masses of galaxies and the masses of the dark matter halos in which they reside. We obtain a parameterized stellar-to-halo mass (SHM) relation by populating halos and subhalos in an N-body simulation with galaxies and requiring that the observed stellar mass function be reproduced. We find good agreement with constraints from galaxy-galaxy lensing and predictions of semi-analytic models. Using this mapping, and the positions of the halos and subhalos obtained from the simulation, we find that our model predictions for the galaxy two-point correlation function (CF) as a function of stellar mass are in excellent agreement with the observed clustering properties in the SDSS at z=0. We show that the clustering data do not provide additional strong constraints on the SHM function and conclude that our model can therefore predict clustering as a function of stellar mass. We compute the conditional mass function, which yields the average number of galaxies with stellar masses in the range [m, m+dm] that reside in a halo of mass M. We study the redshift dependence of the SHM relation and show that, for low mass halos, the SHM ratio is lower at higher redshift. The derived SHM relation is used to predict the stellar mass dependent galaxy CF and bias at high redshift. Our model predicts that not only are massive galaxies more biased than low mass ones at all redshifts, but the bias increases more rapidly with increasing redshift for massive galaxies than for low mass ones. We present convenient fitting functions for the SHM relation as a function of redshift, the conditional mass function, and the bias as a function of stellar mass and redshift.Comment: 21 pages, 17 figures, discussion enlarged, one more figure, updated references, accepted for publication in Ap

An in vivo demonstration of efficacy and acute safety of burst wave lithotripsy using a porcine model

Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6–7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury

Ocean chlorofluorocarbon and heat uptake during the twentieth century in the CCSM3

Author Posting. © American Meteorological Society 2006. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 19 (2006): 2366–2381, doi:10.1175/JCLI3758.1.An ensemble of nine simulations for the climate of the twentieth century has been run using the Community Climate System Model version 3 (CCSM3). Three of these runs also simulate the uptake of chlorofluorocarbon-11 (CFC-11) into the ocean using the protocol from the Ocean Carbon Model Intercomparison Project (OCMIP). Comparison with ocean observations taken between 1980 and 2000 shows that the global CFC-11 uptake is simulated very well. However, there are regional biases, and these are used to identify where too much deep-water formation is occurring in the CCSM3. The differences between the three runs simulating CFC-11 uptake are also briefly documented. The variability in ocean heat content in the 1870 control runs is shown to be only a little smaller than estimates using ocean observations. The ocean heat uptake between 1957 and 1996 in the ensemble is compared to the recent observational estimates of the secular trend. The trend in ocean heat uptake is considerably larger than the natural variability in the 1870 control runs. The heat uptake down to 300 m between 1957 and 1996 varies by a factor of 2 across the ensemble. Some possible reasons for this large spread are discussed. There is much less spread in the heat uptake down to 3 km. On average, the CCSM3 twentieth-century ensemble runs take up 25% more heat than the recent estimate from ocean observations. Possible explanations for this are that the model heat uptake is calculated over the whole ocean, and not just in the regions where there are many observations and that there is no parameterization of the indirect effects of aerosols in CCSM3.Support provided by the National Science Foundation, the Department of Energy, the Ministry of Education, Culture, Sports, Science and Technology, and the Earth Simulator Center of the Japan Agency for Marine- Earth Science and Technology