Training referential communicative skills to individuals with autism spectrum disorder: a pilot study

Summary. The present study reports the effects of referential communication training in individuals formally diagnosed with autism spectrum disorder (ASD). Participants were 20 children with ASD (M age = 14.3 yr., SD = 4.2; 6 girls, 14 boys) in the role of speakers and 20 control children, who acted as listeners. They were all enrolled in mainstream compulsory education. Inclusion/exclusion criteria were defined according to the clinical diagnosis of ASD, the presence or absence of additional or associated disability, previous training in referential communication, and any drug treatment. Speakers were randomly assigned to one of two groups (trained vs untrained). Linguistic age, cognitive level, and autistic symptoms were analyzed, respectively, with the Peabody Picture Vocabulary Test (PPVT), the Wechsler Intelligence Scale (WISCR or WAISIII), and the Autistic Behavior Checklist (ABC). Communicative abilities were analyzed through two indexes related to message complexity and self-regulation. The trained group was trained in referential communication tasks (task analysis, role taking, and task evaluation), while the untrained group took part in a communicative game but without any specific communicative training. The results showed that the complexity of emitted messages had improved statistically significantly in the trained group as an effect of training. Ecological referential communication is shown to be an appropriate paradigm for studying the communicative process and its products and could be used to develop and implement a training program focused on those skills in which individuals with ASD are most deficient.

Is it the grain size or the characteristic pore size that controls the induced polarization relaxation time of clean sands and sandstones?

There is a wide range of evidence to suggest that permeability can be constrained through of induced polarization measurements. For clean sands and sandstones, current mechanistic models of induced polarization predict a relationship between the low-frequency time constant inferred from induced polarization measurements and the grain diameter. A number of observations do, however, disagree with this and indicate that the observed relaxation behavior is rather governed by the so-called dynamic pore radius L. To test this hypothesis, we have developed a set of new scaling relationships, which allow the relaxation time to be computed from the pore size and the permeability to be computed from both the Cole-Cole time constant and the formation factor. Moreover, these new scaling relationships can be also used to predict the dependence of the Cole-Cole time constant as a function of the water saturation under unsaturated conditions. Comparative tests of the proposed new relationships with regard to various published experimental results for saturated clean sands and sandstones as well as for partially saturated clean sandstones, do indeed confirm that the dynamic pore radius L is a much more reliable indicator of the observed relaxation behavior than grain-size-based models.

Activities of fosfomycin, tigecycline, colistin, and gentamicin against extended-spectrum-β-lactamase-producing Escherichia coli in a foreign-body infection model.

Limited antimicrobial agents are available for the treatment of implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli. We compared the activities of fosfomycin, tigecycline, colistin, and gentamicin (alone and in combination) against a CTX-M15-producing strain of Escherichia coli (Bj HDE-1) in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration in logarithmic phase (MBC(log)) and stationary phase (MBC(stat)) were 0.12, 0.12, and 8 μg/ml for fosfomycin, 0.25, 32, and 32 μg/ml for tigecycline, 0.25, 0.5, and 2 μg/ml for colistin, and 2, 8, and 16 μg/ml for gentamicin, respectively. In time-kill studies, colistin showed concentration-dependent activity, but regrowth occurred after 24 h. Fosfomycin demonstrated rapid bactericidal activity at the MIC, and no regrowth occurred. Synergistic activity between fosfomycin and colistin in vitro was observed, with no detectable bacterial counts after 6 h. In animal studies, fosfomycin reduced planktonic counts by 4 log(10) CFU/ml, whereas in combination with colistin, tigecycline, or gentamicin, it reduced counts by >6 log(10) CFU/ml. Fosfomycin was the only single agent which was able to eradicate E. coli biofilms (cure rate, 17% of implanted, infected cages). In combination, colistin plus tigecycline (50%) and fosfomycin plus gentamicin (42%) cured significantly more infected cages than colistin plus gentamicin (33%) or fosfomycin plus tigecycline (25%) (P < 0.05). The combination of fosfomycin plus colistin showed the highest cure rate (67%), which was significantly better than that of fosfomycin alone (P < 0.05). In conclusion, the combination of fosfomycin plus colistin is a promising treatment option for implant-associated infections caused by fluoroquinolone-resistant Gram-negative bacilli.

Single spin-echo T 2 relaxation times of cerebral metabolites at 14.1 T in the in vivo rat brain.

OBJECT: To determine the single spin-echo T 2 relaxation times of uncoupled and J-coupled metabolites in rat brain in vivo at 14.1 T and to compare these results with those previously obtained at 9.4 T. MATERIALS AND METHODS: Measurements were performed on five rats at 14.1 T using the SPECIAL sequence and TE-specific basis-sets for LCModel analysis. RESULTS AND CONCLUSION: The T 2 of singlets ranged from 98 to 148 ms and T 2 of J-coupled metabolites ranged from 72 ms (glutamate) to 97 ms (myo-inositol). When comparing the T 2s of the metabolites measured at 14.1 T with those previously measured at 9.4 T, a decreasing trend was found (p < 0.0001). We conclude that the modest shortening of T 2 at 14.1 T has a negligible impact on the sensitivity of the (1)H MRS when performed at TE shorter than 10 ms.

Cardiac rotation and relaxation in patients with aortic valve stenosis.

BACKGROUND: Diastolic dysfunction with delayed relaxation and abnormal passive elastic properties has been described in patients with severe pressure overload hypertrophy. The purpose of this study was to evaluate the time course of rotational motion of the left ventricle in patients with aortic valve stenosis using myocardial tagging. METHODS: Myocardial tagging is a non-invasive method based on magnetic resonance which makes it possible to label ('tag') specific myocardial regions. From the motion of the tag's cardiac rotation, radial displacement and translational motion can be determined. In 12 controls and 13 patients with severe aortic valve stenosis systolic and diastolic wall motion was assessed in an apical and basal short axis plane. RESULTS: The normal left ventricle performs a systolic wringing motion around the ventricular long axis with clockwise rotation at the base (-4.4+/-1.6 degrees) and counter-clockwise rotation at the apex (+6.8+/-2.5 degrees) when viewed from the apex. During early diastole an untwisting motion can be observed which precedes diastolic filling. In patients with aortic valve stenosis systolic rotation is reduced at the base (-2.4+/-2.0 degrees; P<0.01) but increased at the apex (+12.0+/-6.0 degrees; P<0.05). Diastolic untwisting is delayed and prolonged with a decrease in normalized rotation velocity (-6.9+/-1.1 s(-1)) when compared to controls (-10.7+/-2.2 s(-1); P<0.001). Maximal systolic torsion is 8.0+/-2.1 degrees in controls and 14.1+/-6.4 degrees (P<0.01) in patients with aortic valve stenosis. CONCLUSIONS: Left ventricular pressure overload hypertrophy is associated with a reduction in basal and an increase in apical rotation resulting in increased torsion of the ventricle. Diastolic untwisting is delayed and prolonged. This may explain the occurrence of diastolic dysfunction in patients with severe pressure overload hypertrophy.

Comment on ‘‘Relaxation Kinetics of Nanoscale Indents in a Polymer Glass’’

A Comment on the Letter by A. Knoll, D. Wiesmann, B. Gotsmann, and U. Duerig, published in Physical Review Letter, 2009, vol. 102, p.117801

Changes in the use of broad-spectrum antibiotics after cefepime shortage: a time series analysis.

The original cefepime product was withdrawn from the Swiss market in January 2007, and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa towards carbapenems, ceftazidime and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply, and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs, and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

Mutations in the human UBR1 gene and the associated phenotypic spectrum.

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

Characterizing the connectome in schizophrenia with diffusion spectrum imaging.

Schizophrenia is a complex psychiatric disorder characterized by disabling symptoms and cognitive deficit. Recent neuroimaging findings suggest that large parts of the brain are affected by the disease, and that the capacity of functional integration between brain areas is decreased. In this study we questioned (i) which brain areas underlie the loss of network integration properties observed in the pathology, (ii) what is the topological role of the affected regions within the overall brain network and how this topological status might be altered in patients, and (iii) how white matter properties of tracts connecting affected regions may be disrupted. We acquired diffusion spectrum imaging (a technique sensitive to fiber crossing and slow diffusion compartment) data from 16 schizophrenia patients and 15 healthy controls, and investigated their weighted brain networks. The global connectivity analysis confirmed that patients present disrupted integration and segregation properties. The nodal analysis allowed identifying a distributed set of brain nodes affected in the pathology, including hubs and peripheral areas. To characterize the topological role of this affected core, we investigated the brain network shortest paths layout, and quantified the network damage after targeted attack toward the affected core. The centrality of the affected core was compromised in patients. Moreover the connectivity strength within the affected core, quantified with generalized fractional anisotropy and apparent diffusion coefficient, was altered in patients. Taken together, these findings suggest that the structural alterations and topological decentralization of the affected core might be major mechanisms underlying the schizophrenia dysconnectivity disorder. Hum Brain Mapp, 36:354-366, 2015. © 2014 Wiley Periodicals, Inc.

Nouveau spectre des troubles cognitifs liés à l'infection par le VIH à l'ère des trithérapies [New spectrum of HIV-associated cognitive disorders in the HAART era]

Highly active anti-retroviral therapy (HAART) has almost abolished HIV-related mortality and serious opportunistic diseases; among them, AIDS-related dementia. However, minor forms of cognitive dysfunction, have not disappeared, and even increased in frequency. Ageing of HIV+ patients, insufficient penetration of anti-viral drugs into the brain with continuous low-grade viral production and inflammation may play a role. Minor cognitive dysfunction in HIV infection shares some clinical and pathophysiological features with neuro-degenerative diseases, in particular Alzheimers disease. It can thus be postulated that, such in Alzheimer disease, anti-cholinesterase drugs might also be efficacious in AIDS-related minor cognitive dysfunction. This hypothesis has not been tested yet however A clinical trial using ravistigmine is starting this spring in patients with HIV-associated cognitive dysfunction in Geneva and Lausanne.

3D noise power spectrum applied on clinical mdct scanners: effects of reconstruction algorithms and reconstruction filters

The noise power spectrum (NPS) is the reference metric for understanding the noise content in computed tomography (CT) images. To evaluate the noise properties of clinical multidetector (MDCT) scanners, local 2D and 3D NPSs were computed for different acquisition reconstruction parameters.A 64- and a 128-MDCT scanners were employed. Measurements were performed on a water phantom in axial and helical acquisition modes. CT dose index was identical for both installations. Influence of parameters such as the pitch, the reconstruction filter (soft, standard and bone) and the reconstruction algorithm (filtered-back projection (FBP), adaptive statistical iterative reconstruction (ASIR)) were investigated. Images were also reconstructed in the coronal plane using a reformat process. Then 2D and 3D NPS methods were computed.In axial acquisition mode, the 2D axial NPS showed an important magnitude variation as a function of the z-direction when measured at the phantom center. In helical mode, a directional dependency with lobular shape was observed while the magnitude of the NPS was kept constant. Important effects of the reconstruction filter, pitch and reconstruction algorithm were observed on 3D NPS results for both MDCTs. With ASIR, a reduction of the NPS magnitude and a shift of the NPS peak to the low frequency range were visible. 2D coronal NPS obtained from the reformat images was impacted by the interpolation when compared to 2D coronal NPS obtained from 3D measurements.The noise properties of volume measured in last generation MDCTs was studied using local 3D NPS metric. However, impact of the non-stationarity noise effect may need further investigations.

Energy relaxation in nonlinear one-dimensional lattices

We study energy relaxation in thermalized one-dimensional nonlinear arrays of the Fermi-Pasta-Ulam type. The ends of the thermalized systems are placed in contact with a zero-temperature reservoir via damping forces. Harmonic arrays relax by sequential phonon decay into the cold reservoir, the lower-frequency modes relaxing first. The relaxation pathway for purely anharmonic arrays involves the degradation of higher-energy nonlinear modes into lower-energy ones. The lowest-energy modes are absorbed by the cold reservoir, but a small amount of energy is persistently left behind in the array in the form of almost stationary low-frequency localized modes. Arrays with interactions that contain both a harmonic and an anharmonic contribution exhibit behavior that involves the interplay of phonon modes and breather modes. At long times relaxation is extremely slow due to the spontaneous appearance and persistence of energetic high-frequency stationary breathers. Breather behavior is further ascertained by explicitly injecting a localized excitation into the thermalized arrays and observing the relaxation behavior.

Clinical spectrum of tuberculous optic neuropathy.

PURPOSE: Tuberculous optic neuropathy may follow infection with Mycobacterium tuberculosis or administration of the bacille Calmette-Guerin. However, this condition is not well described in the ophthalmic literature. METHODS: Ophthalmologists, identified through professional electronic networks or previous publications, collected standardized clinical data relating to 62 eyes of 49 patients who they had managed with tuberculous optic neuropathy. RESULTS: Tuberculous optic neuropathy was most commonly manifested as papillitis (51.6 %), neuroretinitis (14.5 %), and optic nerve tubercle (11.3 %). Uveitis was an additional ocular morbidity in 88.7 % of eyes. In 36.7 % of patients, extraocular tuberculosis was present. The majority of patients (69.4 %) had resided in and/or traveled to an endemic area. Although initial visual acuity was 20/50 or worse in 62.9 % of 62 eyes, 76.7 % of 60 eyes followed for a median of 12 months achieved visual acuities of 20/40 or better. Visual field defects were reported for 46.8 % of eyes, but these defects recovered in 63.2 % of 19 eyes with follow-up. CONCLUSION: Visual recovery from tuberculous optic neuropathy is common, if the diagnosis is recognized and appropriate treatment is instituted. A tuberculous etiology should be considered when evaluating optic neuropathy in persons from endemic areas.