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To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438).
We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections.
Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts.
Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
The purpose of this study was to examine how exposure to the armed conflict and the tsunami, perceived availability of resources, and perceived helpfulness of religious practices would predict depression, anxiety, posttraumatic stress, and psychosocial functioning in a multi-ethnic sample of Sri Lankan youth. A sample of Tamil (174), Sinhalese (332), and Muslim (215) children (girls=391) between 12 and 19 years (mean age =14.4, sd =1.9), completed a survey including demographic questions and items assessing exposure to the conflict and the tsunami, the perceived availability of resources, and perceived helpfulness of religious practices. Scales assessing depression, anxiety, posttraumatic stress, and psychosocial functioning were also completed. Four hierarchical multiple regression analyses were conducted with exposure to the conflict and tsunami, perceived availability of resources, and perceived helpfulness of religious beliefs as predictors, and with depression, anxiety, posttraumatic stress and psychosocial functioning as outcomes. The results revealed that exposure to the armed conflict significantly predicted posttraumatic stress (R2 =.03, F [1,494] = 12.77, p< .001), while exposure to the tsunami predicted anxiety (R2 =.03, F [2,506] = 7.8, p< .001), and perceived availability of resources predicted depression (R2=.09, F [4,499] = 11.83, p< .001) and psychosocial functioning (R2=.098, F [4,506] = 13.67, p< .001). The results suggest that exposure to traumatic events should not be assumed to be the only or even the most important variable when considering the overall psychological and psychosocial functioning of children in developing countries and traditional cultures. Implications for interventions, policy, and future research are discussed.
In this paper, a high gain wideband circularly polarized (CP) microstrip antenna is presented for broadband operation. The proposed structure comprised of a partially grounded printed monopole antenna loaded with a split ring resonator and a metallic reflector. By using the metallic reflector surface underneath the patch radiator results in the reflected waves in the same phase with main lobe radiation, thereby improving the gain and it also acts like a secondary radiator to generate wideband CP behavior in the proposed design. A gain enhancement of 4.3 dBi is achieved in the operating frequency band as compared with the design without a metallic reflector. The maximum gain achieved in the presented method is 8.6 dBic over the entire operating range. The proposed design shows a wideband behavior ranging from 4.30 to 9.10 GHz with the 10-dB impedance bandwidth of 71.64%. In addition, the proposed design yielded a broadside right hand CP radiation with a 3-dB axial ratio bandwidth of 33.88% from 4.98 to 7.01 GHz. The proposed antenna is fabricated and experimental results on reflection coefficient, gain, axial ratio, and radiation patterns concede well with simulation results.
Periconceptional folic acid (FA) has an established role in the prevention of neural tube defects (NTDs), leading to global recommendations for FA supplementation before and in early pregnancy. However, it is unclear whether there are any benefits for offspring brain health arising from continued maternal FA supplementation beyond the first trimester. The aim of this study was to investigate the role of maternal folate nutrition during pregnancy in relation to cognitive performance and brain function in the offspring at 11 years. The children of mothers who had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) were investigated, providing a unique opportunity to examine offspring brain health in relation to maternal folate (the FASSTT Offspring trial; n = 68). Cognitive performance was assessed using the Wechsler Intelligence Scale for Children, Fourth UK Edition (WISC-IV). The WISC-IV measures Full Scale IQ and specific domains of cognitive performance: Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed. Brain function was measured using magnetoencephalography (MEG) in a subset of the child participants (n = 33). The results showed no significant difference in Full Scale IQ between the children of mothers who had received folic acid versus placebo during pregnancy (P = 0.993). Processing Speed subtest scores were however significantly higher in the folic acid group compared with placebo (Symbol Search: P = 0.046 and Cancellation: P = 0.011). The application of MEG analysis showed that at rest, there were differences in brain functioning with significantly lower overall power at Broad band [1–48Hz] (P = 0.041) and a trend (not significant) towards lower power in all other frequency bands (Theta, Mu, Beta, Low Gamma and High Gamma) in children from the FA group compared with placebo. Results for the responses to the language task (congruent and incongruent sentences) in children from the FA group showed significantly lower power within the Theta band [4–8Hz] and significantly higher power within high frequency bands i.e. Beta [13–30 Hz] and High Gamma [49–70 Hz]. This suggested more efficient language processing abilities in these children compared to children of mothers in the placebo group. The findings provide scientific evidence that continuing FA supplementation beyond the periconceptional period that is protective against NTDs, may be beneficial for brain health in the offspring. Furthermore, this study demonstrates that MEG is a useful tool for objective assessment of functional brain activity in healthy children in response to nutrition intervention.
Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system.
An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service.
The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be “evidence-based” and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future.
This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.
This study examined the effectiveness of a formal postdoctoral education program designed to teach skills in clinical and translational science, using scholar publication rates as a measure of research productivity.
Participants included 70 clinical fellows who were admitted to a master’s or certificate training program in clinical and translational science from 1999 to 2015 and 70 matched control peers. The primary outcomes were the number of publications 5 years post-fellowship matriculation and time to publishing 15 peer-reviewed manuscripts post-matriculation.
Clinical and translational science program graduates published significantly more peer-reviewed manuscripts at 5 years post-matriculation (median 8 vs 5, p=0.041) and had a faster time to publication of 15 peer-reviewed manuscripts (matched hazard ratio = 2.91, p=0.002). Additionally, program graduates’ publications yielded a significantly higher average H-index (11 vs. 7, p=0.013).
These findings support the effectiveness of formal training programs in clinical and translational science by increasing academic productivity.
The changes in DSM-5 diagnostic criteria for dementia (Major neurocognitive disorder (NCD)) and mild cognitive impairment (mild NCD) mandate a re-evaluation of screening instruments. This study attempted to validate screening instruments, identify optimum threshold, and describe their indices of efficacy.
Consecutive people above the age of 65 years attending the outpatient department of a general hospital were recruited. They were assessed using the Mini-Mental State Examination and the Vellore Screening Instruments for Dementia and were evaluated against the DSM-5 standard. Bivariate and multivariate statistics were obtained. Receiver-operating-characteristic curves were drawn, optimum thresholds obtained, sensitivity, specificity, and predictive values calculated.
One hundred and thirty four older people were recruited. The majority were women, married, with low levels of education, not employed, living with family, and had medical co-morbidity. A minority satisfied DSM-5 criteria for major (1.5%) and mild NCD (36.5%). The factors associated with NCD were older age, fewer years of education, and lower socio-economic status. MMSE, VSID patient, and VSID informant scores were significantly associated with NCD. The indices of efficacy for the MMSE and VSID patient version were modest for identifying Mild NCD. However, their performance in identifying major NCD was better. Nevertheless, optimal thresholds for recognition differed markedly from their originally recommended cut-offs.
The DSM-5 standards, with new and different cognitive domains, mandate a revaluation and recalibration of existing screening instruments. Ideally, new screening instruments, which match the cognitive domains and DSM-5 standard should be developed.
The solar active region (AR) 12192 was one of the most flare productive region of solar cycle 24, which produced many X-class flares; the most energetic being an X3.1 flare on October 24, 2014 at 21:10 UT. Customarily, such events are believed to be triggered by magnetic reconnection in coronal magnetic fields. Here we use the vector magnetograms from solar photosphere, obtained from Heliospheric Magnetic Imager (HMI) to investigate the magnetic field topology prior to the X3.1 event, and ascertain the conditions that might have caused the flare. To infer the coronal magnetic field, a novel non-force-free field (NFFF) extrapolation technique of the photospheric field is used, which suitably mimics the Lorentz forces present in the photospheric plasma. We also highlight the presence of magnetic null points and quasi-separatrix layers (QSLs) in the magnetic field topology, which are preferred sites for magnetic reconnections and discuss the probable reconnection scenarios.
The daily time series Flare Index (FI) data of Northern Hemisphere, Southern Hemisphere and Total Disk for Solar Cycle 21- 23 and 24 up to Dec. 2014 has been pre-processed using a 2nd order exponential smoothing algorithm to remove orthogonal noise. The smoothed data in each case is processed for scaling analysis using Rescaled-Range Analysis as well as Finite Variance Scaling Method in order to search for the Hurst exponent. As the value of H obtained from our analysis lies in between 0 and 1, so it can be said that the signal may behave like Fractional Brownian Motion. Also, it is observed that H is less than 0.5 which indicates the data is anti-persistent in nature and it has a strong negative correlation within the signal. The value of H also indicates the oscillating features of the signal which might have some fundamental periodicities in the Suns atmosphere.
Magnetic reconnections (MRs) for various magnetic field line (MFL) topologies are believed to be the initiators of solar eruptive events like flares and coronal mass ejections (CMEs). Consequently, important is a thorough understanding and quantification of the MFL topology and their evolution which leads to MRs. Contemporary standard is to extrapolate the coronal MFLs using equilibrium models where the Lorentz force on the coronal plasma is zero everywhere. In tandem, a non-force-free-field (NFFF) extrapolation scheme has evolved and allows for a Lorentz force which is non-zero only at the photosphere but asymptotically vanishes with height. The paper reports magnetohydrodynamic (MHD)- simulations initiated by NFFF extrapolation of the coronal MFLs for a flare producing active region NOAA 11158. Interestingly, quasi-separatrix layers (QSLs) which facilitate MRs are detected in the extrapolated MFLs and, here the paper makes an attempt to asses the role of QSLs in the flare onsets.
Artificial Neural Network based Nonlinear Autoregressive Model is designed to reconstruct and predict Forbush Decrease (FD) Data obtained from Izmiran, Russia. Result indicates that the model seems adequate for short term prediction of the FD data.
To compare interrater reliabilities for ventilator-associated event (VAE) surveillance, traditional ventilator-associated pneumonia (VAP) surveillance, and clinical diagnosis of VAP by intensivists.
A retrospective study nested within a prospective multicenter quality improvement study.
Intensive care units (ICUs) within 5 hospitals of the Centers for Disease Control and Prevention Epicenters.
Patients who underwent mechanical ventilation.
We selected 150 charts for review, including all VAEs and traditionally defined VAPs identified during the primary study and randomly selected charts of patients without VAEs or VAPs. Each chart was independently reviewed by 2 research assistants (RAs) for VAEs, 2 hospital infection preventionists (IPs) for traditionally defined VAP, and 2 intensivists for any episodes of pulmonary deterioration. We calculated interrater agreement using κ estimates.
The 150 selected episodes spanned 2,500 ventilator days. In total, 93–96 VAEs were identified by RAs; 31–49 VAPs were identified by IPs, and 29–35 VAPs were diagnosed by intensivists. Interrater reliability between RAs for VAEs was high (κ, 0.71; 95% CI, 0.59–0.81). Agreement between IPs using traditional VAP criteria was slight (κ, 0.12; 95% CI, −0.05–0.29). Agreement between intensivists was slight regarding episodes of pulmonary deterioration (κ 0.22; 95% CI, 0.05–0.39) and was fair regarding whether episodes of deterioration were attributable to clinically defined VAP (κ, 0.34; 95% CI, 0.17–0.51). The clinical correlation between VAE surveillance and intensivists’ clinical assessments was poor.
Prospective surveillance using VAE criteria is more reliable than traditional VAP surveillance and clinical VAP diagnosis; the correlation between VAEs and clinically recognized pulmonary deterioration is poor.
The Institute Ice Stream (IIS) rests on a reverse-sloping bed, extending >150 km upstream into the ~1.8 km deep Robin Subglacial Basin, placing it at the threshold of marine ice-sheet instability. Understanding IIS vulnerability has focused on the effect of grounding-line melting, which is forecast to increase significantly this century. Changes to ice-flow dynamics are also important to IIS stability, yet little is known about them. Here we reveal that the trunk of the IIS occurs downstream of the intersection of three discrete subglacial features; a large ‘active’ subglacial lake, a newly-discovered sharp transition to a zone of weak basal sediments and a major tectonic rift. The border of IIS trunk flow is confined by the sediment on one side, and by a transition between basal melting and freezing at the border with the Bungenstock Ice Rise. By showing how basal sediment and water dictate present-day flow of IIS, we reveal that ice-sheet stability here is dependent on this unusual arrangement.
Background: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Methods: Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. Results: The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. Conclusions: There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.
the maternally inherited MTTL1 A3243G mutation in the mitochondrial genome causes MelaS (Mitochondrial encephalopathy lactic acidosis with Stroke-like episodes), a condition that is multisystemic but affects primarily the nervous system. Significant intra-familial variation in phenotype and severity of disease is well recognized.
retrospective and ongoing study of an extended family carrying the MTTL1 A3243G mutation with multiple symptomatic individuals. tissue heteroplasmy is reviewed based on the clinical presentations, imaging studies, laboratory findings in affected individuals and pathological material obtained at autopsy in two of the family members.
there were seven affected individuals out of thirteen members in this three generation family who each carried the MTTL1 A3243G mutation. the clinical presentations were varied with symptoms ranging from hearing loss, migraines, dementia, seizures, diabetes, visual manifestations, and stroke like episodes. three of the family members are deceased from MelaS or to complications related to MelaS.
the results of the clinical, pathological and radiological findings in this family provide strong support to the current concepts of maternal inheritance, tissue heteroplasmy and molecular pathogenesis in MelaS. neurologists (both adult and paediatric) are the most likely to encounter patients with MelaS in their practice. genetic counselling is complex in view of maternal inheritance and heteroplasmy. newer therapeutic options such as arginine are being used for acute and preventative management of stroke like episodes.