Brainstem, Cardiac Abnormalities and Autonomic Nervous System in Autism

Introduction: Behavioral disorders are the hallmarks of autism spectrum disorders (ASD). Cardiovascular and gastrointestinal dysfunction such as arrhythmias and dyspepsia are also reported in autism. Some research have implicated autonomic nervous system (ANS) comprising the vagus nerve and dorsal motor nucleus in the pathogenesis of ASD.Aim: To examine the changes in ANS in ASD and to investigate biological markers and histopathological specimens associated with ANS.Method: The authors conducted a pathological and biochemical study on brainstem autonomic and cardiac tissues on four autistic cases and four age-matched controls. They quantified inflammatory, neurotransmitter and amino acid-related markers in both the autistic and control tissues. The data was analyzed using SPSSv18 software.Results: There was a significant increase of microglia in the DMV (dorsal motor vagus nucleus), increased astrocytes in area postrema and decreased ubiquitin levels in the medullary region of the brainstem in ASD tissues compared to the controls. (p<0.05). Alterations in biogenic amines and amino acids associated with dopamine metabolism in the cardiac tissues of the autistic cases were also present. Amino acids alanine, cysteine and tyrosine were significantly low in individuals affected by ASD (p< 0.05). 3-methoxytyramine levels were significantly high (p<0.05) in ASD individuals suggesting dopamine pathway dysfunction.Conclusion: The study is in concordance with the concept that autonomic nervous system is affected in individuals with autism spectrum disorders. Cardiovascular and gastrointestinal disturbances could be due to autonomic dysfunction and alteration in amino acid and neurotransmitter metabolism. Further studies are needed to affirm the association

Non-pharmacological solutions to sleep and circadian rhythm disruption: voiced bedside experiences of hospice and end-oflife staff caregivers

Background: Sleep disturbance is a significant issue, particularly for patients with advanced terminal illness. Currently, there are no practice-based recommended approaches for managing sleep and circadian disruptions in this population. To address this gap, a cross-sectional focus group study was performed engaging 32 staff members at four hospices/end-of-life programs in three demographically diverse counties in New York State. Methods: Participants responded to structured open-ended questions. Responses were transcribed and subjected to qualitative content analysis. The themes and recommendations for improved practice that emerged were tabulated using Atlas TI qualitative software. Results: This report details the experiences of hospice and end-of-life care staff in managing sleep and circadian disruptions affecting patients and analyzes their recommendations for improving care. Caregivers involved in the study described potential interventions that would improve sleep and reduce circadian disruptions. They particularly highlighted a need for improved evaluation and monitoring systems, as well as sleep education programs for both formal and informal caregivers. Conclusions: The voiced experiences of frontline hospice and end-of-life caregivers confirmed that disruption in sleep and circadian rhythms is a common issue for their patients and is not effectively addressed in current research and practice. The caregivers’ recommendations focused on management strategies and underscored the need for well-tested interventions to promote sleep in patients receiving end-of-life care. Additional research is needed to examine the effectiveness of systematic programs that can be easily integrated into the end-of-life care process to attenuate sleep disturbances

LoCuSS: A Comparison of Sunyaev-Zel'dovich Effect and Gravitational Lensing Measurements of Galaxy Clusters

We present the first measurement of the relationship between the Sunyaev-Zel'dovich effect signal and the mass of galaxy clusters that uses gravitational lensing to measure cluster mass, based on 14 X-ray luminous clusters at z~0.2 from the Local Cluster Substructure Survey. We measure the integrated Compton y-parameter, Y, and total projected mass of the clusters (M_GL) within a projected clustercentric radius of 350 kpc, corresponding to mean overdensities of 4000-8000 relative to the critical density. We find self-similar scaling between M_GL and Y, with a scatter in mass at fixed Y of 32%. This scatter exceeds that predicted from numerical cluster simulations, however, it is smaller than comparable measurements of the scatter in mass at fixed T_X. We also find no evidence of segregation in Y between disturbed and undisturbed clusters, as had been seen with T_X on the same physical scales. We compare our scaling relation to the Bonamente et al. relation based on mass measurements that assume hydrostatic equilibrium, finding no evidence for a hydrostatic mass bias in cluster cores (M_GL = 0.98+/-0.13 M_HSE), consistent with both predictions from numerical simulations and lensing/X-ray-based measurements of mass-observable scaling relations at larger radii. Overall our results suggest that the Sunyaev-Zel'dovich effect may be less sensitive than X-ray observations to the details of cluster physics in cluster cores.Comment: Minor changes to match published version: 2009 ApJL 701:114-11

Joint analysis of X-ray and Sunyaev Zel'dovich observations of galaxy clusters using an analytic model of the intra-cluster medium

We perform a joint analysis of X-ray and Sunyaev Zel'dovich (SZ) effect data using an analytic model that describes the gas properties of galaxy clusters. The joint analysis allows the measurement of the cluster gas mass fraction profile and Hubble constant independent of cosmological parameters. Weak cosmological priors are used to calculate the overdensity radius within which the gas mass fractions are reported. Such an analysis can provide direct constraints on the evolution of the cluster gas mass fraction with redshift. We validate the model and the joint analysis on high signal-to-noise data from the Chandra X-ray Observatory and the Sunyaev-Zel'dovich Array for two clusters, Abell 2631 and Abell 2204.Comment: ApJ in pres

Sunyaev Zel'dovich Effect Observations of Strong Lensing Galaxy Clusters: Probing the Over-Concentration Problem

We have measured the Sunyaev Zel'dovich (SZ) effect for a sample of ten strong lensing selected galaxy clusters using the Sunyaev Zel'dovich Array (SZA). The SZA is sensitive to structures on spatial scales of a few arcminutes, while the strong lensing mass modeling constrains the mass at small scales (typically < 30"). Combining the two provides information about the projected concentrations of the strong lensing clusters. The Einstein radii we measure are twice as large as expected given the masses inferred from SZ scaling relations. A Monte Carlo simulation indicates that a sample randomly drawn from the expected distribution would have a larger median Einstein radius than the observed clusters about 3% of the time. The implied overconcentration has been noted in previous studies with smaller samples of lensing clusters. It persists for this sample, with the caveat that this could result from a systematic effect such as if the gas fractions of the strong lensing clusters are substantially below what is expected.Comment: submitte

LoCuSS: The Sunyaev-Zel'dovich Effect and Weak Lensing Mass Scaling Relation

We present the first weak-lensing-based scaling relation between galaxy cluster mass, M_wl, and integrated Compton parameter Y_sph. Observations of 18 galaxy clusters at z~0.2 were obtained with the Subaru 8.2-m telescope and the Sunyaev-Zel'dovich Array. The M_wl-Y_sph scaling relations, measured at Delta=500, 1000, and 2500 rho_c, are consistent in slope and normalization with previous results derived under the assumption of hydrostatic equilibrium (HSE). We find an intrinsic scatter in M_wl at fixed Y_sph of 20%, larger than both previous measurements of M_HSE-Y_sph scatter as well as the scatter in true mass at fixed Y_sph found in simulations. Moreover, the scatter in our lensing-based scaling relations is morphology dependent, with 30-40% larger M_wl for undisturbed compared to disturbed clusters at the same Y_sph at r_500. Further examination suggests that the segregation may be explained by the inability of our spherical lens models to faithfully describe the three-dimensional structure of the clusters, in particular, the structure along the line-of-sight. We find that the ellipticity of the brightest cluster galaxy, a proxy for halo orientation, correlates well with the offset in mass from the mean scaling relation, which supports this picture. This provides empirical evidence that line-of-sight projection effects are an important systematic uncertainty in lensing-based scaling relations.Comment: Accepted versio

Comparison of Pressure Profiles of Massive Relaxed Galaxy Clusters using Sunyaev-Zel'dovich and X-ray Data

We present Sunyaev-Zel'dovich (SZ) effect observations of a sample of 25 massive relaxed galaxy clusters observed with the Sunyaev-Zel'dovich Array (SZA), an 8-element interferometer that is part of the Combined Array for Research in Millimeter-wave Astronomy (CARMA). We perform an analysis of new SZA data and archival Chandra observations of this sample to investigate the integrated pressure -- a proxy for cluster mass -- determined from X-ray and SZ observations, two independent probes of the intra-cluster medium. This analysis makes use of a model for the intra-cluster medium introduced by Bulbul (2010) which can be applied simultaneously to SZ and X-ray data. With this model, we estimate the pressure profile for each cluster using a joint analysis of the SZ and X-ray data, and using the SZ data alone. We find that the integrated pressures measured from X-ray and SZ data are consistent. This conclusion is in agreement with recent results obtained using WMAP and Planck data, confirming that SZ and X-ray observations of massive clusters detect the same amount of thermal pressure from the intra-cluster medium. To test for possible biases introduced by our choice of model, we also fit the SZ data using the universal pressure profile proposed by Arnaud (2010), and find consistency between the two models out to r500 in the pressure profiles and integrated pressures.Comment: Accepted for New Journal of Physics, Focus Issue on Galaxy Cluster

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Momentary assessment of interpersonal process in psychotherapy

To demonstrate how a novel computer joystick coding method can illuminate the study of interpersonal processes in psychotherapy sessions, we applied it to Shostrom's (1966) well-known films in which a client, Gloria, had sessions with 3 prominent psychotherapists. The joystick method, which records interpersonal behavior as nearly continuous flows on the plane defined by the interpersonal dimensions of control and affiliation, provides an excellent sampling of variability in each person's interpersonal behavior across the session. More important, it yields extensive information about the temporal dynamics that interrelate clients' and therapists' behaviors. Gloria's 3 psychotherapy sessions were characterized using time-series statistical indices and graphical representations. Results demonstrated that patterns of within-person variability tended to be markedly asymmetric, with a predominant, set-point-like interpersonal style from which deviations mostly occurred in just 1 direction (e.g., occasional submissive departures from a modal dominant style). In addition, across each session, the therapist and client showed strongly cyclical variations in both control and affiliation, and these oscillations were entrained to different extents depending on the therapist. We interpreted different patterns of moment-to-moment complementarity of interpersonal behavior in terms of different therapeutic goals, such as fostering a positive alliance versus disconfirming the client's interpersonal expectations. We also showed how this method can be used to provide a more detailed analysis of specific shorter segments from each of the sessions. Finally, we compared our approach to alternative techniques, such as act-to-act lagged relations and dynamic systems and pointed to a variety of possible research and training applications

Multiplatform molecular test performance in indeterminate thyroid nodules

BackgroundApproximately 25% of thyroid nodule fine‐needle aspirates (FNAs) have cytology that is indeterminate for malignant disease. Accurate risk stratification of these FNAs with ancillary testing would reduce unnecessary thyroid surgery.MethodsWe evaluated the performance of an ancillary multiplatform test (MPTX) that has three diagnostic categories (negative, moderate, and positive). MPTX includes the combination of a mutation panel (ThyGeNEXT®) and a microRNA risk classifier (ThyraMIR®). A blinded, multicenter study was performed using consensus histopathology diagnosis among three pathologists to validate test performance.ResultsUnanimous consensus diagnosis was reached in 197 subjects with indeterminate thyroid nodules; 36% had disease. MPTX had 95% sensitivity (95% CI,86%‐99%) and 90% specificity (95% CI,84%‐95%) for disease in prevalence adjusted nodules with Bethesda III and IV cytology. Negative MPTX results ruledout disease with 97% negative predictive value (NPV; 95% CI,91%‐99%) at a 30% disease prevalence, while positive MPTX results ruledin high risk disease with 75% positive predictive value (PPV; 95% CI,60%‐86%). Such results are expected in four out of five Bethesda III and IV nodules tested, including RAS positive nodules in which the microRNA classifier was useful in rulingin disease. 90% of mutation panel false positives were due to analytically verified RAS mutations detected in benign adenomas. Moderate MPTX results had a moderate rate of disease (39%, 95% CI,23%‐54%), primarily due to RAS mutations, wherein the possibility of disease could not be excluded.ConclusionsOur results emphasize that decisions for surgery should not solely be based on RAS or RAS‐like mutations. MPTX informs management decisions while accounting for these challenges.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163550/2/dc24564_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163550/1/dc24564.pd