Deprivation of Social Play: Implications for the Mechanisms of Autism Spectrum Disorders

Social play emerges in early adolescence and is one of the primary types of social interaction seen early in life in mammals. The experience of social play is essential for the normal trajectory of social and cognitive development. Adolescent mammals deprived opportunities for social interaction at this age display neurodevelopmental abnormalities. Social deprivation alters adult behavioral patterns, neuroanatomy, and neurochemistry in ways that resemble autism spectrum disorder (ASD). These deficits include impairments in communication, social perception, and social behavior. However, the symptom most characteristic of the earliest stage of ASD is decreased interest in social objects. Understanding the role of early social experience, especially play, in the development of social, cognitive, and emotional functioning will provide insight into the development of ASD. In order to understand how social deprivation can affect behavior, researchers isolate animals during early adolescence. Most studies have looked at rodents since it appears that isolation-rearing of rodents has detrimental effects on social development, making it a valid model of ASD. This chapter will consider the potential of this model as a model of ASD, and how it can inform understanding of ASD and the neurodevelopmental mechanisms altered by reduced social interactions early in life

Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice

The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows noninvasive in vivo assessment of drug-modulated local cerebral blood volume changes (ΔCBV) as one correlate of neuronal and neurovascular activities. In this report, we employed CBV-weighted phMRI to compare cocaine-modulated neuronal activity in dopamine transporter (DAT) knockout (KO) and wild-typemice. Cocaine acts to block the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT) that clear their respective neurotransmitters from the synapses, helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV, with a similar pattern of regional ΔCBV in brain structures involved inmediating reward in both DAT genotypes. The largest effects (−20% to −30% ΔCBV) were seen in the nucleus accumbens and several cortical regions. Decreasing response amplitudes to cocaine were noted in more posterior components of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated ΔCBV amplitudes, shortened times to peak response, and reduced response duration in most regions. This study demonstrates that DAT knockout does not abolish the phMRI responses to cocaine, suggesting that adaptations to loss of DAT and/or retained cocaine activity in other monoamine neurotransmitter systems underlie these responses in DAT KO mice

Adjunctive intravitreal dexamethasone in the treatment of acute endophthalmitis following cataract surgery

Edward F Hall1, Garrett R Scott1, David C Musch1,2, David N Zacks11Department of Ophthalmology and Visual Sciences, Medical School; 2Department of Epidemiology, School of Public Health; University of Michigan, Ann Arbor, MI, USAPurpose: Controversy exists regarding the use of intravitreal dexamethasone (IVD) as an anti-inflammatory adjunct to intravitreal antibiotics in patients with acute endophthalmitis following cataract surgery. The purpose of this project was to evaluate our experience regarding the effect of adjunctive IVD use on visual outcomes in such patients.Design: Retrospective, comparative case series.Methods: Study population: Patients treated for acute endophthalmitis following cataract surgery from 1995–2004. Intervention: In addition to standard intravitreal antibiotic treatment, some patients also received a single adjunctive injection of IVD. Primary outcome measures: Median visual acuity at last follow-up and percentage of patients achieving a ≥3-line improvement in visual acuity. Secondary outcome measures: Inflammatory index scoring, including amount of cell and flare, height of hypopyon, and presence of fibrin as a function of time after treatment.Results: Twenty-six eyes were treated with and 38 eyes without adjunctive IVD. Median presenting visual acuity was Hand Motion in both groups. Median visual acuity at last followup measured 20/40 in the IVD group and 20/50 in the No-IVD group (p = 0.75). Seventy-three percent of patients in the IVD group and 82% of patients in the No-IVD group achieved a ≥3-line improvement in visual acuity (p = 0.42). No significant difference was detected between the IVD and No-IVD groups for any of the three measures of inflammation.Conclusion: The use of IVD did not significantly improve the final median visual acuity, the chance of achieving a ≥3-line improvement in visual acuity, or the amount of intraocular inflammation. Based on these findings, and the possible detrimental effect of IVD on visual outcomes previously reported in the literature, the use of IVD does not appear to be warranted as a routine adjunctive treatment in postoperative endophthalmitis.Keywords: endophthalmitis, dexamethasone, intravitreal injectio

X-ray Insights into the Nature of Quasars with Redshifted Broad Absorption Lines

We present $Chandra$ observations of seven broad absorption line (BAL) quasars at $z=0.863$-2.516 with redshifted BAL troughs (RSBALs). Five of our seven targets were detected by $Chandra$ in 4-13 ks exposures with ACIS-S. The $\alpha_{\rm ox}$ values, $\Delta\alpha_{\rm ox}$ values, and spectral energy distributions of our targets demonstrate they are all X-ray weak relative to expectations for non-BAL quasars, and the degree of X-ray weakness is consistent with that of appropriately-matched BAL quasars generally. Furthermore, our five detected targets show evidence for hard X-ray spectral shapes with a stacked effective power-law photon index of $\Gamma_{\rm eff}=0.5^{+0.5}_{-0.4}$. These findings support the presence of heavy X-ray absorption ($N_{\rm H}\approx 2 \times 10^{23}$ cm$^{-2}$) in RSBAL quasars, likely by the shielding gas found to be common in BAL quasars more generally. We use these X-ray measurements to assess models for the nature of RSBAL quasars, finding that a rotationally-dominated outflow model is favored while an infall model also remains plausible with some stipulations. The X-ray data disfavor a binary quasar model for RSBAL quasars in general.Comment: 11 pages, 5 figures, and 3 table

Chandra X-Ray Observations of Two Unusual BAL Quasars

We report sensitive Chandra X-ray non-detections of two unusual, luminous Iron Low-Ionization Broad Absorption Line Quasars (FeLoBALs). The observations do detect a non-BAL, wide-binary companion quasar to one of the FeLoBAL quasars. We combine X-ray-derived column density lower limits (assuming solar metallicity) with column densities measured from ultraviolet spectra and CLOUDY photoionization simulations to explore whether constant density slabs at broad line region densities can match the physical parameters of these two BAL outflows, and find that they cannot. In the "overlapping-trough" object SDSS J0300+0048, we measure the column density of the X-ray absorbing gas to be N_H >= 1.8 x 1024 cm-2. From the presence of Fe II UV78 absorption but lack of Fe II UV195/UV196 absorption, we infer the density in that part of the absorbing region to be n_e ~ 106 cm-3. We do find that a slab of gas at that density might be able to explain this object's absorption. In the Fe III-dominant object SDSS J2215-0045, the X-ray absorbing column density of N_H >= 3.4 x 1024 cm-2 is consistent with the Fe III-derived N_H >= 2 x 1022 cm-2 provided the ionization parameter is log U > 1.0 for both the n_e = 1011 cm-3 and n_e = 1012 cm-3 scenarios considered (such densities are required to produce Fe III absorption without Fe II absorption). However, the velocity width of the absorption rules out its being concentrated in a single slab at these densities. Instead, this object's spectrum can be explained by a low density, high ionization and high temperature disk wind that encounters and ablates higher density, lower ionization Fe III-emitting clumps.Comment: 18 pages, 6 figure

The incidence and clinical burden of respiratory syncytial virus disease identified through hospital outpatient presentations in Kenyan children

There is little information that describe the burden of respiratory syncytial virus (RSV) associated disease in the tropical African outpatient setting. Methods We studied a systematic sample of children aged <5 years presenting to a rural district hospital in Kenya with acute respiratory infection (ARI) between May 2002 and April 2004. We collected clinical data and screened nasal wash samples for RSV antigen by immunofluorescence. We used a linked demographic surveillance system to estimate disease incidence. Results Among 2143 children tested, 166 (8%) were RSV positive (6% among children with upper respiratory tract infection and 12% among children with lower respiratory tract infection (LRTI). RSV was more likely in LRTI than URTI (p<0.001). 51% of RSV cases were aged 1 year or over. RSV cases represented 3.4% of hospital outpatient presentations. Relative to RSV negative cases, RSV positive cases were more likely to have crackles (RR = 1.63; 95% CI 1.34–1.97), nasal flaring (RR = 2.66; 95% CI 1.40–5.04), in-drawing (RR = 2.24; 95% CI 1.47–3.40), fast breathing for age (RR = 1.34; 95% CI 1.03–1.75) and fever (RR = 1.54; 95% CI 1.33–1.80). The estimated incidence of RSV-ARI and RSV-LRTI, per 100,000 child years, among those aged <5 years was 767 and 283, respectively. Conclusion The burden of childhood RSV-associated URTI and LRTI presenting to outpatients in this setting is considerable. The clinical features of cases associated with an RSV infection were more severe than cases without an RSV diagnosis

Magnetic White Dwarfs from the SDSS II. The Second and Third Data Releases

Fifty-two magnetic white dwarfs have been identified in spectroscopic observations from the Sloan Digital Sky Survey (SDSS) obtained between mid-2002 and the end of 2004, including Data Releases 2 and 3. Though not as numerous nor as diverse as the discoveries from the first Data Release, the collection exhibits polar field strengths ranging from 1.5MG to ~1000MG, and includes two new unusual atomic DQA examples, a molecular DQ, and five stars that show hydrogen in fields above 500MG. The highest-field example, SDSSJ2346+3853, may be the most strongly magnetic white dwarf yet discovered. Analysis of the photometric data indicates that the magnetic sample spans the same temperature range as for nonmagnetic white dwarfs from the SDSS, and support is found for previous claims that magnetic white dwarfs tend to have larger masses than their nonmagnetic counterparts. A glaring exception to this trend is the apparently low-gravity object SDSSJ0933+1022, which may have a history involving a close binary companion.Comment: 20 pages, 4 figures Accepted for publication in the Astronomical Journa

Evolution of Mosquito-Based Arbovirus Surveillance Systems in Australia

Control of arboviral disease is dependent on the sensitive and timely detection of elevated virus activity or the identification of emergent or exotic viruses. The emergence of Japanese encephalitis virus (JEV) in northern Australia revealed numerous problems with performing arbovirus surveillance in remote locations. A sentinel pig programme detected JEV activity, although there were a number of financial, logistical, diagnostic and ethical limitations. A system was developed which detected viral RNA in mosquitoes collected by solar or propane powered CO2-baited traps. However, this method was hampered by trap-component malfunction, microbial contamination and large mosquito numbers which overwhelmed diagnostic capabilities. A novel approach involves allowing mosquitoes within a box trap to probe a sugar-baited nucleic-acid preservation card that is processed for expectorated arboviruses. In a longitudinal field trial, both Ross River and Barmah Forest viruses were detected numerous times from multiple traps over different weeks. Further refinements, including the development of unpowered traps and use of yeast-generated CO2, could enhance the applicability of this system to remote locations. New diagnostic technology, such as next generation sequencing and biosensors, will increase the capacity for recognizing emergent or exotic viruses, while cloud computing platforms will facilitate rapid dissemination of data

Evolution of Mosquito-Based Arbovirus Surveillance Systems in Australia

Control of arboviral disease is dependent on the sensitive and timely detection of elevated virus activity or the identification of emergent or exotic viruses. The emergence of Japanese encephalitis virus (JEV) in northern Australia revealed numerous problems with performing arbovirus surveillance in remote locations. A sentinel pig programme detected JEV activity, although there were a number of financial, logistical, diagnostic and ethical limitations. A system was developed which detected viral RNA in mosquitoes collected by solar or propane powered CO2-baited traps. However, this method was hampered by trap-component malfunction, microbial contamination and large mosquito numbers which overwhelmed diagnostic capabilities. A novel approach involves allowing mosquitoes within a box trap to probe a sugar-baited nucleic-acid preservation card that is processed for expectorated arboviruses. In a longitudinal field trial, both Ross River and Barmah Forest viruses were detected numerous times from multiple traps over different weeks. Further refinements, including the development of unpowered traps and use of yeast-generated CO2, could enhance the applicability of this system to remote locations. New diagnostic technology, such as next generation sequencing and biosensors, will increase the capacity for recognizing emergent or exotic viruses, while cloud computing platforms will facilitate rapid dissemination of data

Evolution of mosquito-based arbovirus surveillance systems in Australia

Control of arboviral disease is dependent on the sensitive and timely detection of elevated virus activity or the identification of emergent or exotic viruses. The emergence of Japanese encephalitis virus (JEV) in northern Australia revealed numerous problems with performing arbovirus surveillance in remote locations. A sentinel pig programme detected JEV activity, although there were a number of financial, logistical, diagnostic and ethical limitations. A system was developed which detected viral RNA in mosquitoes collected by solar or propane powered CO₂-baited traps. However, this method was hampered by trap-component malfunction, microbial contamination and large mosquito numbers which overwhelmed diagnostic capabilities. A novel approach involves allowing mosquitoes within a box trap to probe a sugar-baited nucleic-acid preservation card that is processed for expectorated arboviruses. In a longitudinal field trial, both Ross River and Barmah Forest viruses were detected numerous times from multiple traps over different weeks. Further refinements, including the development of unpowered traps and use of yeast-generated CO₂, could enhance the applicability of this system to remote locations. New diagnostic technology, such as next generation sequencing and biosensors, will increase the capacity for recognizing emergent or exotic viruses, while cloud computing platforms will facilitate rapid dissemination of data