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The Canada Health Act requires reasonable access to all medically necessary therapies. No information is available to assess the current access to neuromodulation across Canada. This study quantifies the current rate of deep brain stimulation (DBS) for the entire country of Canada. Analyses were performed to determine whether there were differences in access based on provincial or territorial location, rural or non-rural region, or socioeconomic status.
All implanted DBS devices in Canada over a 2-year epoch (January 2015 to December 2016) were supplied by either Boston Scientific or Medtronic. Investigators received anonymized data from these companies, including patient age and home residence region. The 2016 Statistics Canada census data were used to determine the rate of DBS surgery and whether access was related to provincial location, rural versus non-rural region or socioeconomic status.
A total of 722 patients were studied. The rate of DBS surgery for the entire country was ten per million population per year. Saskatchewan was significantly above (374%) the national average, whereas Quebec (40%) and Newfoundland & Labrador (32%) were significantly below the national average. No patients from the three territories received DBS. There were no significant differences in access from rural versus non-rural areas or in regions within provinces with different socioeconomic status.
This is the first study to quantify all patients receiving DBS within an entire country. The current rate of DBS surgery within Canada is ten cases per million per year. Statistically significant regional differences were discovered and discussed.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters.
Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71).
Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs.
This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.
Current group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored.
Hierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575).
Three qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently.
Quantitative SZ–BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors.
Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis.
A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1–3, posterior CA1–3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability.
Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans.
This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.
Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 s.d. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not.
A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning.
Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia.
These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment.
There is a considerable scarcity of reliable population-based data on the prevalence of preventable ear disorders in developing countries. This study was conducted to determine the prevalence of preventable ear disorders in primary school children (aged 5 to 12 years) in northern India.
A pro forma questionnaire was used to screen 15 718 primary school children in New Delhi for ear disorders. Ear examinations were conducted using otoscopy and impedance audiometry.
Impacted cerumen was prevalent in 7.93 per cent of schoolchildren, 4.79 per cent suffered from chronic otitis media and 3.06 per cent suffered from otitis media with effusion. Acute otitis media was detected in 0.65 per cent and foreign bodies were found in 0.34 per cent of the children.
Preventable ear diseases posed a significant health problem among children at primary school level. Regular screening of children during this stage would ensure that their school lives were not affected by hearing impairments or preventable ear disorders. Information gathered in this study will help in effective treatment prioritisation of ear disorders, planning and resource allocation.
Cognitive deficits are core to the disability associated with many psychiatric disorders. Both variation in cognition and psychiatric risk show substantial heritability, with overlapping genetic variants contributing to both. Unsurprisingly, therefore, these fields have been mutually beneficial: just as cognitive studies of psychiatric risk variants may identify genes involved in cognition, so too can genome-wide studies based on cognitive phenotypes lead to genes relevant to psychiatric aetiology. The purpose of this review is to consider the main issues involved in the phenotypic characterization of cognition, and to describe the challenges associated with the transition to genome-wide approaches. We conclude by describing the approaches currently being taken by the international consortia involving many investigators in the field internationally (e.g. Cognitive Genomics Consortium; COGENT) to overcome these challenges.
Irradiation of vapor-deposited C60 films with a KeV ion beam (Ar+ or Ga+) transforms the surface layer of C60 into a non-volatile carbon film. During the subsequent annealing at 900°C, the modified C60 layer confines the underlying C60 on the silicon surface, allowing the formation of SiC. With this method, patterned SiC structures on silicon with the high lateral resolution possible with ion beams are fabricated
We demonstrate that picosecond ultrasonics provides detailed information on the structure and properties of patterned arrays of copper fine lines used in silicon chip interconnections. In this method, the sample surface is momentarily heated several °C using a pump laser beam, and the transient change in the optical reflectivity is measured by a probe laser beam. Measurements of the optical reflectivity are made on time scales ranging from picoseconds to nanoseconds, revealing information on electronic, acoustic and thermal properties. We have applied this method to samples consisting of copper line arrays of 0.4 µm linewidth, 0.65 µm pitch and 0.35 µm depth in SiO2 on silicon wafers. For comparison, we examined the picosecond ultrasonic response of 200 nm-thick blanket copper thin films. The patterned Cu lines are found to have long-term oscillations at frequencies of 4.39 and 8.29 GHz with lifetimes at least 10 times longer than the oscillations in the blanket Cu film. A two-dimensional mechanical analysis was developed which uses as input parameters the dimensions and sound velocities of the materials in the sample, and finds the normal mode frequencies and displacements. The main vibrational modes are identified and described for the patterned lines, and the simulations confirm that the lowest frequency modes have very small damping coefficients. Also, the time-dependent signal is shown to reveal details of interface layers and integrity of the copper/liner interface.
We have developed a new cluster ion source that can generate intense beams of metal and semiconductor clusters of a very wide-size range. With the source, we have observed intense beams of carbon clusters with mean cluster sizes of up to 4000 atoms/clusters. However, we have found that for generating small fullerenes, such as C60 and C70, the recently discovered technique by Kraetschmer et al. is much more efficient. By improving the technique, we have generated gram quantities of C60 and C70 and systematically investigated their thermal desorption properties. During the heating process, we have discovered that at high temperatures the bulk fullerenes, fullerite, transformed to another form of carbon, which still evaporates at temperatures above 700 C, but does not dissolve in benzene.
Comparative differential scanning calorimetry (DSC) measurements were made at 200 K < T < 310 K on geometrically restricted cyclohexane and n-decane in nude-, trimethyl derivatized-, and hexyl derivatized-porous (Rp = 4 nm) silica with a view to determine how the surface structure of the confining media affects the thermodynamic behavior of the restricted fluid. Our results suggest that, irrespective of the fact that both trimethyl derivatized- and hexyl derivatized-silica have methyl terminal groups, the freezing or melting transition of cyclohexane is much more depressed in trimethyl derivatized-silica than in hexyl derivatized- or nude-silica. This is not the case for n-decane where the depression in the melting transition is consistent with the fact that the effective pore radius of the hexyl derivatized-silica is smaller than the trimethyl derivatized- or nude-silica.
Sputtered Mo films with a thickness of 2μm or greater have been previously shown by xray and TEM studies to grow with strong in-plane and out-of-plane textures under dynamic deposition conditions. In this work, the geometric conditions and mechanisms causing preferential grain alignment in the plane of growth for sputtered Mo films, with a nominal thickness of 2μm, were explored. Four different deposition configurations, obtained by varying the parameters such as the deposition angle and the rotation speed of the substrates, were used in order to modify the texture as studied by x-ray and SEM techniques. While a  type out-of-plane texture was observed for all four deposition configurations, a (110) type in-plane texture, and the corresponding grain alignment in the plane of growth, was observed only when the flux of adatoms was hitting the substrates at an oblique angle. The texture characteristics and the microstructure of the Mo films, as analyzed using the pole figure x-ray and SEM techniques, were observed to be very similar for films deposited on three different substrates, namely the Si(100) and Ni3Al(321) single crystals, and laboratory grade glass slides. The in-plane texture development under oblique deposition conditions was proposed to be due to a combination of two mechanisms, namely the preferential resputtering of some of the grains normal to and in the plane of growth caused by the higher energy adatoms in the flux, followed by termination of the preferentially sputtered grains due to geometric shadowing.
Pulsed laser deposited cerium oxide (CeO2) nanoporous thin film on platinum (Pt) coated glass has been used for immobilization of glucose oxidase (GOx) by electrostatic interaction. Atomic force microscopy studies reveal the formation of nanoporous surface morphology of CeO2 thin film. Differential pulse voltammetric and optical measurements show that the GOx/CeO2/Pt bioelectrode is sensitive to the detection of glucose over the concentration upto 300 mg/dl. A low value of enzyme's kinetic parameter (Michaelis-Menten constant∼1.01 mM) indicates enhanced enzyme affinity of GOx to glucose.
Incidence of colourblindness among 3325 males belonging to 21 endogamous Dhangar castes (shepherds) of Maharashtra, India, has been reported. Of the 21 castes studied 5 lacked the gene for colourblindness, while in other groups it varied from 1% to 55%, with a series average of 2·65%. The low incidence of observed colourblindness has been discussed in the light of the nomadic way of the life of some of the Dhangar castes. The results have been compared with other nomadic populations of Maharashtra. The results, in general, are compatible with the Post and Pickford's hypothesis of differential selection for colourblindness.