To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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 is a copy of the slides presented at the meeting but not formally written up for the volume.
Nanomedicine encompasses a vast area of biomedical research, from the development of new generation of contrast agents for diagnostic imaging to synthesizing targeted delivery vehicles of therapeutic drugs. This talk will highlight the use of multifunctional nanoparticles with combined imaging, diagnostic and therapeutic functions for nanomedicine. In our Institute we are developing new optical nanoprobes for bioimaging. They include functionalized quantum dots, aggregation-enhanced two photon dyes as well as nanocomposite nanoparticles with combined optical, magnetic, plasmonic and PET imaging capabilities. The goal is to provide targeting nanoprobes for early detection of diseases as well as for real time monitoring of a disease progression or the progress of a therapy. The organically modified silica (ORMOSIL) nanoparticles have been developed as a new-generation drug carrier for photodynamic therapy (PDT) of cancer, as well as for an efficient non-viral gene delivery, capable of transfecting neuronal cells in vivo with superior efficacy over viral vectors.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Proteomics based clinical diagnostics systems utilize the principle of protein identification as a means of biomarker profiling for disease diagnosis. The current standardized immunoassay techniques such as Enzyme linked Immunosorbent Assays (ELISA) are based on the fluorescent detection of the antibody (Ab)-antigen (Ag) binding event. These techniques are expensive; time consuming requiring a large sample volume. We present here two electrical immunoassay techniques that can potentially used for the rapid, multiplexed diagnosis of proteins for disease identification. The first technique involves the use of nanoporous templates in conjunction with microfabricated platforms with metallic base electrodes resulting In the formation of a “nanowell” assay system that is analogous to the micro titer well plate system. The detection of the formation of binding complex is achieved by capacitive measurement techniques. The dynamic range and the calibration of the device has been performed with respective to the current gold standard in proteomics. The second technique involves the use of microscale carriers to transport ab’s to sensing sites on microfabricated base platforms. The binding of the Ag’s to the Ab’s coupled to the carriers’ results in measurable voltage changes that are recorded in a real time manner. The calibration and the dynamic range of this device has also been determined. Both these techniques demonstrate potential as early diagnostic devices and their performance in detection of clinically relevant proteins is demonstrated.
In 1955, J. Surányi and P. Turán (8) initiated the problem of existence and uniqueness of interpolatory polynomials of degrees less than or equal to 2n — 1 when their values and second derivatives are prescribed on n given nodes. This kind of interpolation was termed (0, 2)-interpolation. Later, Balázs and Turán (1) gave the explicit representation of the interpolatory polynomials for the case when the n given nodes (n even) are taken to be the zeros of πn(x) = (1 — x2)Pn′(x), where Pn–i(x) is the Legendre polynomial of degree n — 1. In this case the explicit representation of interpolatory polynomials turns out to be simple and elegant.
Balázs and Turán (2) proved the convergence of these polynomials when f(x) has a continuous first derivative satisfying certain conditions of modulus of continuity. They noted (1) that a significant application of lacunary interpolation could possibly be given in the theory of a differential equation of the form y′ + A(x)y= 0.
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.
Pulse chunies are popular agro-industrial byproducts, obtained from processing of pulses in the preparation of dals and are available to extent of 3 million tonnes in India. These chunies comprise broken seed coat, germ and small pieces of broken cotyledons and constitute about 15-20% of total weight of pulse seeds. Very little information is available in the literature on effective levels of inclusion of chunies in complete rations for ruminants. An attempt was made to study the effect of inclusion of varying levels of urad (Vigna mungo) chuni in the concentrate mixtures on the nutrient utilization in native male buffaloes.
Pulse chunies are byproducts obtained from processing of pulses while preparing dals and are available to an extent of 3 million tonnes annually in India. They contain broken seed coat, germ and small pieces of broken cotyledons constituting around 15-20% of total weight of pulses. Very little information is available in the literature on effective levels of inclusion of chunies in complete rations for ruminants. The objective of this experiment was to study the effect of inclusion of varying levels of green gram (Vigna radiata) Chuni in the concentrate mixtures for native buffaloes on the nutrient utilization.
A new digital elevation model of the surface of the Greenland ice sheet and surrounding rock outcrops has been produced from a comprehensive suite of satellite and airborne remote-sensing and cartographic datasets. The surface model has been regridded to a resolution of 5 km, and combined with a new ice-thickness grid derived from ice-penetrating radar data collected in the 1970s and 1990s. A further dataset, the International Bathymetric Chart of the Arctic Ocean, was used to extend the bed elevations to include the continental shelf. The new bed topography was compared with a previous version used for ice-sheet modelling. Near the margins of the ice sheet and, in particular, in the vicinity of small-scale features associated with outlet glaciers and rapid ice motion, significant differences were noted. This was highlighted by a detailed comparison of the bed topography around the northeast Greenland ice stream.
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.