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Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
To characterise subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence.
Questionnaires assessing symptom severity and impact on function and quality of life were administered to patients before superior semicircular canal dehiscence surgery, between June 2011 and March 2016. Questionnaire sections included general quality of life, internal amplified sounds, dizziness and tinnitus, with scores of 0–100 points.
Twenty-three patients completed the questionnaire before surgery. Section scores (mean±standard deviation) were: 38.2 ± 25.2 for general quality of life, 52.5 ± 23.9 for internal amplified sounds, 35.1 ± 28.8 for dizziness, 33.3 ± 30.7 for tinnitus, and 39.8 ± 22.2 for the composite score. Cronbach's α statistic averaged 0.93 (range, 0.84–0.97) across section scores, and 0.83 for the composite score.
The Gopen–Yang Superior Semicircular Canal Dehiscence Questionnaire provides a holistic, patient-centred characterisation of superior semicircular canal dehiscence symptoms. Internal consistency analysis validated the questionnaire and provided a quantitative framework for further optimisation in the clinical setting.
To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate.
Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth.
Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis.
There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.
This paper presents a novel method to determine the workspace of parallel manipulators using a variant of the Firefly Algorithm, which is one of the emerging techniques in swarm artificial intelligence. The workspace is defined as a set of all the coordinates in the search space that are accessible by the parallel manipulator end effector. The workspace formulation of the parallel manipulator considered in this paper has actuated and passive joint displacements which values are limited by their physical constraints. A special fitness function that discriminates between accessible and inaccessible coordinates is formulated based on the joint limitations. By finding these coordinates using the proposed Firefly Algorithm, the workspace of the manipulator can be constructed. The proposed method is an easy-to-implement alternative solution to the current numerical methods for workspace determination. The method consists of two stages of operation. The first stage maps the workspace to find the initial results with a space filling approach, in which a number of coordinates in the workspace are identified. The second stage refines the results with a boundary detection approach which focuses on the mapping of the boundaries of the workspace. The method is illustrated by its application to determine the 2D, 3D, and 6D workspaces of a Gough--Stewart Platform manipulator. Furthermore, the method is compared with a more rigorous interval analysis method in terms of computational cost and accuracy.
Exposure to a maternal junk food (JF) diet in utero and during the suckling period has been demonstrated to increase the preference for palatable food and increase the susceptibility to diet-induced obesity in adult offspring. We aimed to determine whether the effects of prenatal exposure to JF could be ameliorated by cross-fostering offspring onto dams consuming a standard rodent chow during the suckling period. We report here that when all offspring were given free access to the JF diet for 7 weeks from 10 weeks of age, male offspring of control (C) or JF dams that were cross-fostered at birth onto JF dams (C-JF, JF-JF), exhibited higher fat (C-C: 12.3 ± 0.34 g/kg/day; C-JF: 14.7 ± 1.04 g/kg/day; JF-C: 11.5 ± 0.41 g/kg/day; JF-JF: 14.0 ± 0.44 g/kg/day; P < 0.05) and overall energy intake (C-C: 930.1 ± 18.56 kJ/kg/day; C-JF: 1029.0 ± 82.9 kJ/kg/day; JF-C: 878.3 ± 19.5 kJ/kg/day; JF-JF: 1003.4 ± 25.97 kJ/kg/day; P < 0.05) than offspring exposed to the JF diet only before birth (JF-C) or not at all (C-C). Female offspring suckled by JF dams, despite no differences in food intake, had increased fat mass as percentage of body weight (C-C: 19.9 ± 1.33%; C-JF: 22.8 ± 1.57%; JF-C: 17.4 ± 1.03%; JF-JF: 22.0 ± 1.0%; P < 0.05) after 3 weeks on the JF diet. No difference in fat mass was observed in male offspring. These findings suggest that the effects of prenatal exposure to a JF diet on food preferences in females and susceptibility to diet-induced obesity in males can be prevented by improved nutrition during the suckling period.
A cross-sectional study was conducted from 10 January to 9 April 2012, to determine the seroprevalence of tuberculosis (TB) of all captive Asian elephants and their handlers in six locations in Peninsular Malaysia. In addition, trunk-wash samples were examined for tubercle bacillus by culture and polymerase chain reaction (PCR). For 63 elephants and 149 elephant handlers, TB seroprevalence was estimated at 20·4% and 24·8%, respectively. From 151 trunk-wash samples, 24 acid-fast isolates were obtained, 23 of which were identified by hsp65-based sequencing as non-tuberculous mycobacteria. The Mycobacterium tuberculosis-specific PCR was positive in the trunk-wash samples from three elephants which were also seropositive. Conversely, the trunk wash from seven seropositive elephants were PCR negative. Hence, there was evidence of active and latent TB in the elephants and the high seroprevalence in the elephants and their handlers suggests frequent, close contact, two-way transmission between animals and humans within confined workplaces.
One of the major contributing factors to the continuous rise in obesity rates is the increase in caloric intake, which is driven to a large extent by the ease of access and availability of palatable high-fat, high-sugar ‘junk foods’. It is also clear that some individuals are more likely to overindulge in these foods than others; however, the factors that determine an individual's susceptibility towards the overconsumption of palatable foods are not well understood. There is growing evidence that an increased preference for these foods may have its origins early in life. Recent work from our group and others has reported that in utero and early life exposure to these palatable foods in rodents increased the offspring's preference towards foods high in fat and sugar. One of the potential mechanisms underlying the programming of food preferences is the altered development of the mesolimbic reward system, a system that plays an important role in driving palatable food intake in adults. The aim of this review is to explore the current knowledge of the programming of food preferences, a relatively new and emerging area in the DOHAD field, with a particular focus on maternal overnutrition, the development of the mesolimbic reward system and the biological mechanisms which may account for the early origins of an increased preference for palatable foods.
Ninety-five patients with recurrent pyogenic cholangitis had a range of specimens taken at laparotomy for bacterial culture. Bacteria were isolated from 68 % of cases. Escherichia coli was the predominant pathogen. Other aerobic and anaerobic intestinal bacteria were also isolated. Liver biopsy, bile and gallstones were the most rewarding specimens for culture. Infection was usually localized, but systemic infection occurred occasionally. The site of infection is probably in the liver parenchyma; however, the route by which intestinal bacteria invade the liver is not known. Sixty per cent of the cases of recurrent pyogenic cholangitis had gallstones and 20% were infected with Clonorchis sinensis.
Strains of Escherichia coli were isolated from laparotomy specimens from Chinese patients with recurrent pyogenic cholangitis in Hong Kong. A large variety of serotypes were found. Several sites were sampled in each patient. While only one serotype was normally isolated from one site, different sites often yielded different serotypes in the same patient. Generally the ‘O’ types found did not correspond to those found in the faeces of the Hong Kong Chinese population.
A non-linear wave propagation mechanism is found for ionization fronts. The fronts propagate due to ionizing collisions between electrons and neutrals. A parameter is obtained which specifies the amount of electrical interaction. For small electrical interaction, charge separation may occur and the front can propagate at any speed greater than a critical value. For large electrical interaction, the number densities of ions and electrons are nearly equal and a lower bound on the propagation speed is also found.
A nonlinear Alfvén wave structure with axial symmetry about the line of force of an ambient magnetic field is presented. The solitary wave forms a ‘ring’ shaped waveguide along the magnetic field line.
The propagation and stability of ion and electron drift waves in a non-homogeneous plasma containing impurity ions is considered. It is shown that the presence of impurities in the plasma may significantly affect the stability criteria of these low frequency waves. Furthermore, perturbations at frequencies which are multiples of the impurity ion cyclotron frequency may also be unstable when ½K2u R21 > 1.
Often one is interested in the electrical conductivity of a plasma for frequencies of the applied electric field comparable to or greater than the effective collision frequency. For the purpose of obtaining an order of magnitude estimate of the conductivity a Lorentz gas model with a Fokker–Planck collision term is used. For this simple model a formula for the a.c. electrical conductivity for two limiting cases is derived in closed form. The first term of the expression for the conductivity in the case where w/k is very large agrees with that obtained by Bernstein & Trehan (1960) for the spatially homogeneous case, while the effect of the spatial gradients is indicated in the higher order terms. In the case where w and k are both equal to zero the expression for the d.c. electrical conductivity of Spitzer (1962) is recovered.
The effect of weak collisions on ion-acoustic wave instabifities in a plasma with large ratios of electron to ion temperatures is investigated. The critical current for instability is shown to be signfficantly reduced by collisions. At the critical current the instability first occurs at non-zero values of kλe. As kλe increases the collisional effects become less and less significant.
The influence of collisions on the universal instability in a fully ionized in- homogeneous plasma is investigated by means of a simplified Fokker-Planck kinetic equation. For the Fokker-Planck model yields results qualitatively similar to the Bhatnagar-Gross-Krook model, but the two models give different collisional effects in the case where b ≥ 1. Further it is shown that collisions in general enhance the temperature gradient instability in a plasma when b ≪ 1 and reduce it when b ≥ 1.
A gastroenteritis outbreak occurred in a military camp where a laboratory and epidemiological investigation was carried out. The early onset of symptoms indicated probable food contamination with Clostridium perfringens. Stool samples collected from affected patients were tested within 4 h via real-time polymerase chain reaction (PCR) for the presence of the C. perfringens plc gene. Ten out of the 12 stool samples were positive. Confirmation of the molecular test results was carried out by enumeration of C. perfringens in stool by culture and shown to be in excess of 106 spores/g stool. The isolates obtained from culture were further analysed by PCR for the presence of the chromosomal enterotoxin (cpe) gene. Based on the clinical symptoms, epidemiological and laboratory investigations, C. perfringens was implicated as the aetiological agent. The ability to conduct real-time PCR analysis greatly shortens the time to diagnosis and allows for preventive and control measures to be effected quickly.