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.
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Background: Calcium (Ca) and magnesium (Mg) are crucial in metabolism, excitability and neuroglial plasticity. Our aim was to evaluate whether Mg (20 mg/kg) or Ca (100 mg/kg) could improve the memory prognosis in the kainic model of mesial temporal epilepsy. Methods: Seizures were induced by systemic injection of kainate (8mg/kg) and mice were then treated by ions every 48 hours. A placebo (physiological solution) replaced kainate or ions in specific groups. Six cohorts were studied for seven weeks: control group (G0: no kainate and no ion, only placebo); untreated reference group (GR: kainate and then placebo); G1 groups were treated from the third day (G1m, G1c: kainate and then Mg/Ca); G2 groups were treated from the third week (G2m, G2c: kainate and then Mg/Ca). Radial maze and a classic maze were used for cognition evaluation. Results: The memory (short/long term) was differently affected by kainate or improved by Mg/Ca. The treated groups performed better than GR mice, but Mg was more effective. In addition, Mg demonstrated an increasing therapeutic effect over time while Ca showed an acute and apparently decreasing action in the G1c group. Conclusions: Mg should be considered for a clinical evaluation of its effect on epileptic disorders.
The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.
Ethics in post-medieval responses to the Middle Ages form the main focus of this volume. The six opening essays tackle such issues as the legitimacy of reinventing medieval customs and ideas, at what point the production and enjoyment of caricaturizing the Middle Ages become inappropriate, how medievalists treat disadvantaged communities, and the tension between political action and ethics in medievalism. The eight subsequent articles then build on this foundation as they concentrate on capitalist motives for melding superficially incompatible narratives in medievalist video games, Dan Brown's use of Dante's Inferno to promote a positivist, transhumanist agenda, disjunctures from medieval literature to medievalist film in portrayals of human sacrifice, the influence of Beowulf on horror films and vice versa, portrayals of war in Beowulf films, socialism in William Morris's translation of Beowulf, bias in Charles Alfred Stothard's Monumental Effigies of Great Britain, and a medieval source for death in the Harry Potter novels. The volume as a whole invites and informs a much larger discussion on such vital issues as the ethical choices medievalists make, the implications of those choices for their makers, and the impact of those choices on the world around us. Karl Fugelso is Professor of Art History at Towson University in Baltimore, Maryland. Contributors: Mary R. Bowman, Harry Brown, Louise D'Arcens, Alison Gulley, Nickolas Haydock, Lisa Hicks, Lesley E. Jacobs, Michael R. Kightley, Phillip Lindley, Pascal J. Massie, Lauryn S. Mayer, Brent Moberley, Kevin Moberley, Daniel-Raymond Nadon, Jason Pitruzello, Nancy M. Resh, Carol L. Robinson, Christopher Roman, M.J. Toswell.
To describe a relatively unknown clinical entity – inflammatory cast of the tympanic membrane after acute otitis media – and its simple out-patient treatment.
Retrospective review of case series.
Subspecialty practice at a tertiary hospital.
Seven patients diagnosed previously with acute otitis media with perforation or otitis externa, and with persistent ear discomfort.
Retrospective chart review.
The patients presented with weeks to months of persistent hearing loss after acute otitis media with perforation or acute otitis externa. Visits to their primary care physicians had been uninformative. After comparison of the affected and unaffected tympanic membranes, a thin, hard cast was identified and removed from the affected tympanic membrane. Improvement in hearing was documented in the three patients who underwent audiometric testing; the remainder had subjective improvement without audiometric evaluation.
Otolaryngologists should be aware of the possibility of an inflammatory cast of the tympanic membrane following acute otitis media with perforation or otitis externa, and should carefully compare the unaffected and affected ears in such cases. Treatment – removal of the rigid cast – is both simple and effective.
The influence of negative substrate bias on the chemical, electrical and mechanical properties of silicon carbide (SiC) thin films deposited onto (100) silicon substrate by dc magnetron cosputtering without external substrate heating is reported. These studies were performed by using the following techniques: Rutherford backscattering spectroscopy (RBS), profilometry, Raman spectroscopy, four-point probe method and nanoindentation. The results indicate that there is a good correlation between the substrate bias voltage and the argon incorporation into SiC film, namely, the SiC films deposited under substrate bias of –200 V and –300 V have higher argon content and higher elastic modulus and hardness than those deposited at 0 V. An opposite behavior was found for electrical resistivity: the SiC deposited at –300 V has resistivity of 0.45 Ω.cm whereas the deposited at 0 V has 7.0 Ω.cm.
This paper reports the deposition of titanium dioxide thin films on p-type
Si(100) substrates using two techniques called conventional magnetron
sputtering (CMS) and hollow cathode magnetron sputtering (HCMS). The
influence of the plasma parameters on the film characteristics (topography,
morphology and crystallinity) was investigated. Films were deposited at
different oxygen concentrations (in the Ar + O2 gas mixture) and axial
distances for fixed values of working pressure (5.0 mTorr) and DC power
(55 W). They were analyzed by profilometry, AFM and XRD. The gas discharge
was diagnosed by single Langmuir probe and OES. Under experimental
conditions used in this work, results show that HCMS favors the growing of
rutile phase due to the increase of the energy on the film surface caused by
the hollow cathode effect. On the other hand, films deposited by CMS present
preferentially anatase phase due to the low energy transferred to the
growing film. Further studies regarding the influence of plasma properties
on the films formation were done in order to understand the plasma-surface
Cylindrical hollow cathode magnetron sputtering (HCMS) system was used to
deposit crystalline titanium dioxide thin films on p-Si (100) substrates.
For a fixed pressure of 0.6 Pa total gas flow rate of 20 sccm and power of
55 W, the influence of the oxygen percentage in the Ar+O2 gas mixture on
the structural and surface properties of the films was studied by
profilometry, XRD and AFM. The substrates were placed inside the hollow
cathode at different positions along its symmetrical axis. Numerical
simulations of cathode ion collection probability (CICP) were done in order
to compare calculated data with the deposition process characteristics. The
results indicate that the deposition rate and the surface roughness
gradually decrease with the distance from the bottom of the cathode, due to
the decrease of the CICP. The increase of the oxygen percentage in the gas
discharge influences directly the deposition rate and decrease the surface
roughness. The XRD analyses show that all the films are crystalline with
predominant anatase (101) and rutile (110) orientations.
In this paper an overview is given on recent results obtained in the framework of an Italian/Croatian collaboration aimed to explore the potential of techniques based on focused MeV ion beams to locally modify the structural, electrical and optical features of diamond.
Experiments were carried out using light (H, He, C) ion beams with energies of the order of MeV, focused to micrometer-size spot and raster scanned onto the surface of monocrystalline (IIa or Ib) diamond samples. Different energies, ion species and fluences were used, in conjunction with variable thickness masks and post annealing processes, to define three-dimensional structures in diamond, whose electrical/optical/structural properties have been suitably characterized. Finite element numerical methods have been employed in the modeling of the material modification and in device design.
Semiconductor nanowires are attractive nano- building blocks for microelectronics. However, the requirements for their manufacturing and application in the microelectronics industry are very demanding. Beyond compatibility with Si technology, full control on the characteristics of the grown wires (diameter, location, crystallinity, etc..), homogeneity on wafer –scale and reproducibility are essential. In this study we review critically important challenges for a controlled process of In –mediated growth of Si nanowires. First, we stress the importance of surface type for both particle catalysts and growth substrates. Both selection and preparation of such surfaces have large impact on growth, as they influence the initiation and the driving forces for the VLS growth mechanism. Moreover, wire characteristics such as morphology, crystalline quality and growth orientation appear more difficult to control when growing from particles with sizes below 40-50nm. This limitation arises as a result of both fundamental mechanisms and more specific constrains linked to the In-Si system.
A few perspectives are given for the achievement of a controlled Si nanowire growth in a Si –technology compatible fashion.