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An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Vortex-induced vibration (VIV) is an important physical phenomenon as one design a riser or a cylindrical structure in ocean. As the riser or the cylindrical structure is adjacent to a seabed, the boundary effect on VIV is not fully understood yet. The direct-forcing immersed boundary (DFIB) method is used to investigate a two-degree-of-freedom VIV of a flexible supported circular cylinder adjacent to a plane boundary in this study. Furthermore, the effect of the VIV of cylinder on skin friction of the plane boundary is investigated. The effects of varying reduced velocity and gap ratio on VIV are discussed. Only a single vortex street is found when the cylinder is close to plane boundary. Hydrodynamic coefficients of the freely vibrating cylinder are analyzed in time and spectral domains. Furthermore, nearly round oval-shaped motion is observed as the so-called lock-in phenomenon occurs. The skin friction of the plane boundary is predicted by the DFIB model. Results show that the vibrating cylinder in the boundary layer flow can reduce the friction effectively. This proposed DFIB model can be useful for the investigation of VIV of the structures under the plane boundary effect even for a small gap between the cylinder and the boundary.
Rotavirus (RV) infection causes acute infantile diarrhoea in humans and animals and remains a major concern for vaccine development. The close proximity of humans to animals may foster cross-species infection resulting in the emergence of novel/unusual strains by genetic reassortment. In this study, we characterized 500 diarrhoeal samples for group A rotaviruses (RVA) from children (n = 290), piglets (n = 95) and calves (n = 115) in Northeast India during 2012–2013. The data showed that 142/500 (28·4%) faecal samples were positive for RVA with the highest level of infection detected in piglets (57/142, 40·1%) followed by children (51/142, 35·9%) and calves (34/142, 23·9%). Sequence-based G- and P-typing showed G1P (25%) and G1P (35%) were the prevailing genotypes in both humans and animals. Single cases of unusual genotypes, i.e. G9P, G5P in humans and G1P, G1P and G3P in animals were also identified. Cluster analyses of the sequences showed regional strains were genetically closer to their homologous strains. However, human G5P and porcine G1P strains showed homology to heterologous hosts of their prototype strains. The subsequent global spread of unusual RV strains may result in their establishment over time, presenting challenges to future vaccine evaluation programmes. More studies on emerging genotypes are required to elucidate how RVA strains evolve post-vaccination. This study supports the need for continuous surveillance of RVA infections after detecting from diverse hosts in a common setting.
Drinking raw date palm sap is the primary route of Nipah virus (NiV) transmission from bats to people in Bangladesh; subsequent person-to-person transmission is common. During December 2010 to March 2011, we investigated NiV epidemiology by interviewing cases using structured questionnaires, in-depth interviews, and group discussions to collect clinical and exposure histories. We conducted a case-control study to identify risk factors for transmission. We identified 43 cases; 23 were laboratory-confirmed and 20 probable. Thirty-eight (88%) cases died. Drinking raw date palm sap and contact with an infected person were major risk factors; one healthcare worker was infected and for another case transmission apparently occurred through contact with a corpse. In absence of these risk factors, apparent routes of transmission included drinking fermented date palm sap. For the first time, a case was detected in eastern Bangladesh. Identification of new epidemiological characteristics emphasizes the importance of continued NiV surveillance and case investigation.
Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.
The West Virginia University Hot hELIcon eXperiment (HELIX) provides variable density and ion temperature plasmas, with controllable levels of thermal anisotropy, for space relevant laboratory experiments in the Large Experiment on Instabilities and Anisotropy (LEIA) as well as fundamental studies of helicon source physics in HELIX. Through auxiliary ion heating, the ion temperature anisotropy (T⊥/T∥) is variable from 1 to 20 for parallel plasma beta (β = 8πnkTi∥/B2) values that span the range of 0.0001 to 0.01 in LEIA. The ion velocity distribution function is measured throughout the discharge volume in steady-state and pulsed plasmas with laser induced fluorescence (LIF). The wavelengths of very short wavelength electrostatic fluctuations are measured with a coherent microwave scattering system. Operating at low neutral pressures triggers spontaneous formation of a current-free electric double layer. Ion acceleration through the double layer is detected through LIF. LIF-based velocity space tomography of the accelerated beam provides a two-dimensional mapping of the bulk and beam ion distribution functions. The driving frequency for the m = 1 helical antenna is continuously variable from 8.5 to 16 MHz and frequency dependent variations of the RF coupling to the plasma allow the spontaneously appearing double layers to be turned on and off without modifying the plasma collisionality or magnetic field geometry. Single and multi-species plasmas are created with argon, helium, nitrogen, krypton, and xenon. The noble gas plasmas have steep neutral density gradients, with ionization levels reaching 100% in the core of the plasma source. The large plasma density in the source enables the study of Aflvén waves in the HELIX device.
Socio-behavioural factors and pathogens associated with childhood diarrhoea are of global public health concern. Our survey in 696 children aged ⩽2 years in rural West Bengal detected rotavirus as sole pathogen in 8% (17/199) of diarrhoeic stool specimens. Other organisms were detected along with rotavirus in 11% of faecal specimens. A third of the children with rotavirus diarrhoea, according to Vesikari score, had severe illness. The top four rotavirus genotypes were G9P (28%), G1P (19%), G2P (14%) and G8P (8%). In the multivariate model, the practice of ‘drawing drinking water by dipping a pot in the storage vessel’ [adjusted odds ratio (aOR) 2·21, 95% confidence interval (CI) 1·03–4·74, P = 0·041], and ‘children aged ⩽6 months with non-exclusive breastfeeding’ (aOR 2·07, 95% CI 1·1–3·82, P = 0·024) had twice the odds of having diarrhoea. Incidence of rotavirus diarrhoea was 24/100 child-years in children aged >6–18 months, 19/100 child-years in children aged >18–24 months and 5/100 child-years in those aged ⩽6 months. Results have translational implications for future interventions including vaccine development.
The effect of discharge voltage on bi-Maxwellian electrons in the diffusion region of a double plasma device has been studied. The increase in discharge voltage enhances the flux of ionizing electrons to the diffusion region separated by a mesh grid. This energetic electron flux in turn affects other important parameters such as density, electron temperature, plasma potential and floating potential in the diffusion region. Furthermore, the dependence of density and temperature of both ionizing and plasma electrons on discharge voltage is investigated. The electron energy probability function obtained from probe data also indicates the bi-Maxwellian nature of electrons.
Unprecedented high rates of anthrax outbreaks have been observed recently in cattle and humans in Bangladesh, with 607 human cases in 2010. By enrolling 15 case and 15 control cattle smallholdings in the spatial zone in July–September 2010, we conducted a case-control study, data of which were analysed by matched-pair analysis and multivariable conditional logistic regression. Feeding animals with uprooted and unwashed grass [odds ratio (OR) 41·2, 95% confidence interval (CI) 3·7–458·8, P=0·003], and feeding water hyacinth (Eichhornia crassipes) (OR 22·2, 95% CI 1·2–418·7, P=0·039) were independent risk factors for anthrax in cattle.
Analyses of sulphur isotope compositions in sedimentary pyrites from the Vindhyan, Chattisgarh and Cuddapah basins show heavy δ34S (> +25 ‰) values during the Mesoproterozoic. The data provide evidence in support of a hypothesized global Proterozoic sulphidic anoxic ocean where very low concentrations of marine sulphate, bacterially reduced in closed systems, produced δ34S values in pyrites similar to or even heavier than marine sulphate. The extreme environmental conditions induced by these anoxic oceans could have been responsible for the delayed oxygenation of the biosphere and retarded evolution of multicellular life.
The characteristics of the specularly reflected laser light (1.06 μm) from a copper plasma have been studied experimentally. The diffusivity and depolarization of specularly reflected radiation can be explained by the density contours and self-generated magnetic field at the radiation turning point in the plasma layer.
Horsegram (Macrotyloma uniflorum) is sown late in the rainy season by resource-poor farmers in marginal, drought-prone areas of India. Sowing and early crop growth coincide with declining rainfall so crop establishment is often poor and yields are low. Horsegram is a ‘neglected’ crop and farmers' choice of varieties to grow is limited to poor-yielding landraces or to modern varieties for which access to seed is limited. In on-station trials, we compared the yield and relative merits over three years of seven varieties potentially suited to conditions in Jharkhand State and sown with or without priming by soaking seeds in water prior to sowing. Yield stability of the varieties was tested using data from these and five additional trials. Farmers' opinions were recorded during six participatory exercises based on farmers' trials, and their rankings were compared with those from the on-station evaluations. Significant variety × year interactions were observed and yield was generally inversely proportional to drought. Both linear and non-linear genotype × environment interactions were significant for all varieties. Variety BK 1 was the most desirable with stable yields across environments and a higher overall mean grain yield. Variety VLG 1 was unresponsive to more favourable environments but yielded more in the low yielding environments. However, it was the earliest to mature and was identified as a promising variety, which farmers preferred for its grain and brown seeds. This could be used to diversify farming systems with additional options for farmers. Although soaking seeds for 12 h was most effective in increasing germination in an in vitro study, soaking for 8 h before sowing increased emergence and final stand by 11 % and grain yield by 10 % averaged over all varieties and years. Soaking advanced flowering by 1.3 d and maturity by 1.9 d. All varieties responded positively to soaking and did so in all three years, although the response was stronger in drier years.
A maize-breeding programme was targeted at resource-poor farmers of eastern India using a client-oriented approach (often called participatory plant breeding). Farmers tested a range of varieties in a participatory varietal selection programme but none proved to be very popular. Information from these trials was used in a breeding programme to develop a broadly-based population from three yellow- and three white-grained maize varieties that were either identified in the trials or had traits liked by farmers. The population was subjected to several cycles of random mating. In the C3, C4 and C6 cycles, subpopulations were extracted and subjected to mass selection over several generations in environments that represented well the target population of environments of resource-poor farmers' fields in eastern India for traits identified by farmers. To identify better the required traits, in some generations the selection was carried out by farmers on a research farm under fertility levels that approximated farmers' practice. The improvement of the subpopulations resulted in several varieties that performed well in research station and on-farm trials. One of them, BVM 2, was released in Jharkhand state, India. In multilocational research station trials, it yielded more than the control variety BM 1 but silked earlier. In the less favourable environments of on-farm trials, its yield superiority, in percentage terms, was higher. Farmers perceived BVM 2 to have better grain quality and stover yield than the local varieties. BVM 2 was specifically bred to meet the needs of the clients (resource-poor farmers with no access to irrigation) and has earlier maturity combined with higher grain yield. The returns were higher from this highly client-oriented approach, than by classical breeding, mainly because uptake was faster as a result of research and extension being done in tandem.
Human ability to manipulate atoms and molecules on quantum basis has generated a new dimension of physical structures for molecular scale transistors and devices. We will discuss about nanodimensional single electron transistor. This molecular device works as a switching element by controlling the electron tunneling for amplifying the current. The basic structure consists of two tunnel junctions isolated by a common insulator of nanodimensional length.
One broader aspect of nano power electronics is that, it has got significant role in nanodimensional device regime as tunneling diodes. They have got inherently fast tunneling rate, which makes them highly suitable for high-speed operation. A special type of tunneling diode is an interband tunneling diode (ITD), which is actually, a p-n diode. The V-I characteristics of such diodes are dependent upon the tunneling barrier and tunneling process itself. Another special feature of these diodes is their negative-differential-resistance characteristics. This special characteristic of such diodes makes them very useful in switching digital circuits.
InGaN/GaN MQW samples were grown by metal organic chemical vapor deposition (MOCVD) on (10-1-1) oriented GaN templates. Effects of growth temperature and reactor pressure on the photoluminescence (PL) properties were investigated. The emission intensity improved significantly when the QWs were grown at 100 Torr, compared to higher pressure growths. The effect of well-width on the luminescence properties was investigated and an optimum well width of 40 Å was determined. Excitation dependent PL measurements revealed no shift in the PL emission wavelength suggesting the absence of electric field in the quantum wells. Furthermore, LEDs fabricated on (1011) GaN templates, emitting at 439 nm, showed no shift in the EL emission wavelength with the increase in drive current, reconfirming the absence of polarization.
A new method is presented, based on the discrete Fourier Transform, for the design of aperiodic lattices to be used in photonic bandgap engineering. Designing an aperiodic lattice by randomly choosing defects is unlikely to result in useful optical transmission characteristics. By contrast, this new method allows an aperiodic lattice to be designed directly from the desired optical characteristic. The use of this method is illustrated with a design for a structure to realise two transmission wavelengths in the stopband of a one-dimensional photonic lattice. This design has been fabricated in silicon-on-insulator and some optical characteristics are given.