Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

SF-36 includes less Parkinson Disease (PD)-targeted content but is more responsive to change than two PD-targeted health-related quality of life measures

To compare validity including responsiveness, and internal consistency reliability and scaling assumptions of a generic (SF-36) and Parkinson Disease (PD)-targeted (PDQ-39; PDQUALIF) health-related quality of life (HRQOL) measures. Ninety-six PD patients were administered for all HRQOL measures by telephonic interview at baseline and 18 months. Relative efficiency and responsiveness were compared relative to four external criteria (self-ratings of PD’s daily effects, global Quality of Life, PD symptom severity, and a depression screener). We examined whether PD-targeted measures explained unique variance beyond the SF-36 by regressing criterion variables on HRQOL scales/items. Adequacy of PD-targeted measures’ original scaling was explored by item-scale correlations. Relative efficiency estimates were similar for generic and PD-targeted measures across all criteria. Responsiveness analyses showed that the SF-36 yielded large (>0.8) effect sizes (ES) for three of eight scales for each of two criterion variables, compared to only one large ES for any scale in either PD-targeted measure. Adjusted R 2 increased from 14 to 27% in regression models that included PD-targeted items compared to models with only SF-36 scales. Item-scale correlations showed significant cross-loading of items across scales of the PD-targeted measures. SF-36 responsiveness was better than that of two PD-targeted measures, yet those measures had content that significantly explains PD patients’ HRQOL

Muscle activation during gait in children with Duchenne muscular dystrophy

The aim of this prospective study was to investigate changes in muscle activity during gait in children with Duchenne muscular Dystrophy (DMD). Dynamic surface electromyography recordings (EMGs) of 16 children with DMD and pathological gait were compared with those of 15 control children. The activity of the rectus femoris (RF), vastus lateralis (VL), medial hamstrings (HS), tibialis anterior (TA) and gastrocnemius soleus (GAS) muscles was recorded and analysed quantitatively and qualitatively. The overall muscle activity in the children with DMD was significantly different from that of the control group. Percentage activation amplitudes of RF, HS and TA were greater throughout the gait cycle in the children with DMD and the timing of GAS activity differed from the control children. Significantly greater muscle coactivation was found in the children with DMD. There were no significant differences between sides. Since the motor command is normal in DMD, the hyper-activity and co-contractions likely compensate for gait instability and muscle weakness, however may have negative consequences on the muscles and may increase the energy cost of gait. Simple rehabilitative strategies such as targeted physical therapies may improve stability and thus the pattern of muscle activity

Effects of insurance status on children's access to specialty care: a systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The current climate of rising health care costs has led many health insurance programs to limit benefits, which may be problematic for children needing specialty care. Findings from pediatric primary care may not transfer to pediatric specialty care because pediatric specialists are often located in academic medical centers where institutional rules determine accepted insurance. Furthermore, coverage for pediatric specialty care may vary more widely due to systematic differences in inclusion on preferred provider lists, lack of availability in staff model HMOs, and requirements for referral. Our objective was to review the literature on the effects of insurance status on children's access to specialty care.</p> <p>Methods</p> <p>We conducted a systematic review of original research published between January 1, 1992 and July 31, 2006. Searches were performed using Pubmed.</p> <p>Results</p> <p>Of 30 articles identified, the majority use number of specialty visits or referrals to measure access. Uninsured children have poorer access to specialty care than insured children. Children with public coverage have better access to specialty care than uninsured children, but poorer access compared to privately insured children. Findings on the effects of managed care are mixed.</p> <p>Conclusion</p> <p>Insurance coverage is clearly an important factor in children's access to specialty care. However, we cannot determine the structure of insurance that leads to the best use of appropriate, quality care by children. Research about specific characteristics of health plans and effects on health outcomes is needed to determine a structure of insurance coverage that provides optimal access to specialty care for children.</p

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.

Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date

Optimizing Field Data Collection for Individual Tree Attribute Predictions Using Active Learning Methods

Light detection and ranging (lidar) data are nowadays a standard data source in studies related to forest ecology and environmental mapping. Medium/high point density lidar data allow to automatically detect individual tree crowns (ITCs), and they provide useful information to predict stem diameter and aboveground biomass of each tree represented by a detected ITC. However, acquisition of field data is necessary for the construction of prediction models that relate field data to lidar data and for validation of such models. When working at ITC level, field data collection is often expensive and time-consuming as accurate tree positions are needed. Active learning (AL) can be very useful in this context as it helps to select the optimal field trees to be measured, reducing the field data collection cost. In this study, we propose a new method of AL for regression based on the minimization of the field data collection cost in terms of distance to navigate between field sample trees, and accuracy in terms of root mean square error of the predictions. The developed method is applied to the prediction of diameter at breast heights (DBH) and aboveground biomass (AGB) of individual trees by using their height and crown diameter as independent variables and support vector regression. The proposed method was tested on two boreal forest datasets, and the obtained results show the effectiveness of the proposed selecting strategy to provide substantial improvements over the different iterations compared to a random selection. The obtained RMSE of DBH/AGB for the first dataset was 5.09 cm/95.5 kg with a cost equal to 8256/6173 m by using the proposed multi-objective method of selection. However, by using a random selection, the RMSE was 5.20 cm/102.1 kg with a cost equal to 28,391/30,086 m. The proposed approach can be efficient in order to get more accurate predictions with smaller costs, especially when a large forest area with no previous field data is subject to inventory and analysis

Deferred acceptance algorithms: history, theory, practice, and open questions

Matching, Market design, Gale-shapley, Deferred acceptance,