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Background: We assessed long-term health-related quality of life (HRQoL) and functioning in adults receiving onabotulinumtoxinA for CM. Methods: Interim analysis of multicentre, prospective, observational study in adults naïve to botulinum toxin (NCT02502123). Mean change from baseline in Migraine-Specific Quality of Life (MSQ) score (primary); healthcare resource utilization (HRU) and work productivity (secondary) assessed in patients receiving 4 of 7 onabotulinumtoxinA treatments (Tx4; ~10 months). Results: Across treatments (baseline, n=196, post-Tx2, n=173, post-Tx4, n=137), the mean (SD) between-session interval and onabotulinumtoxinA dose was 13.1 weeks and 170.4 (17.2) U, respectively. MSQ scores increased significantly (P<0.0001) (baseline to post-Tx4; all role function domains). Patient percentages declined from baseline to post-Tx2 and post-Tx4 for emergency room visits (17.3%; 9.3%; 6.6%), hospital admissions (3.6%; 2.9%; 1.5%), and headache-related diagnostic testing (35.9%; 15.9%; 8.1%). The percentages of patients employed at baseline (73.5%) and post-Tx4 (72.3%) were similar. Hours worked increased slightly from baseline to post-Tx4 (28.0 [SD=15.4]; 29.4 [SD=16.0]). Headache-related missed work hours decreased (5.9 [SD=9.5]; 2.5 [SD=5.9]). Patients reported less headache-related impact on work productivity from baseline to post-Tx4 (5.4 [SD=2.1] vs 3.9 [SD=2.6]) and ability to perform daily activities (6.1 [SD=2.1] vs 4.2 [SD=2.8]). Conclusions: OnabotulinumtoxinA for CM improved HRQoL and work productivity and reduced HRU.
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.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
The computerized fluorescence radiation induced energy dispersive analyzer (FRIEDA) (1) described earlier uses an x-ray beam with a well defined energy for the excitation of fluorescence radiation, and an Si(Li) detector to measure the total x-ray spectra emitted. Such a system can also simultaneously provide supplemental data for the determination of the dry mass and the sample mass absorption which is necessary for accurate quantitation of the results. This instrumental capabillty has been utilized in the measurement of the trace elements iron, copper, and zinc in serum.
Known amounts of two elements are thoroughly mixed with the sample. One element has a ‘high energy’ K line, the other a ‘low energy’ K line. The ratio of these intensities, in the absence of absorption, is a known constant and dependent only on the relative amounts of the respective elements, and on the energy of the exciting radiation. Whenever absorption is present, the ratio will change in a manner directly related to the mass absorption of the sample for these radiations.
A computerized systetn, consisting of a fluorescence x-ray source (Philips), an Si (Li) detector (Ortec), and a mini Computer (Xerox) is currentiy in operation at The University of Texas M. D. Anderson Hospital and Tumor Institute, Experimentel Pathology Section, for the analysis of trace elements in biological specimens. The elements of interest are Fe, Cu, and Zn for possible significance in the detection and study of cancer. The detection system is being used for comparatively routine analysis of these elements, which are present in blood serum in the ppM range. With appropriate sample preparation techniques, using 1 ml of serum, the limit of detectability for these elements is estimated to be 100 ppB (1 in 107). Further refinement is possible, and research in this direction continues.
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.
The objectives of this study were to compare the quality-of-life scores of Malaysian children with CHD and their healthy siblings, to determine the level of agreement between proxy-reports and child self-reports, and to examine variables that have an impact on quality of life in those with CHD.
Parental-proxy scores of the Pediatric Quality of Life Inventory 4.0 core scales were obtained for 179 children with CHD and 172 siblings. Intra-class coefficients were derived to determine the levels of proxy–child agreement in 66 children aged 8–18 years. Multiple regression analysis was used to determine factors that impacted Pediatric Quality of Life Inventory scores.
Proxy scores were lower in children with CHD than siblings for all scales except physical health. Maximum differences were noted in children aged 5–7 years, whereas there were no significant differences in the 2–4 and 13–18 years age groups. Good levels of proxy–child agreement were found in children aged 8–12 years for total, psychosocial health, social, and school functioning scales (correlation coefficients 0.7–0.8). In children aged 13–18 years, the level of agreement was poor to fair for emotional and social functioning. The need for future surgery and severity of symptoms were associated with lower scores.
Differences in proxy perception of quality of life appear to be age related. The level of proxy–child agreement was higher compared with other reported studies, with lower levels of agreement in teenagers. Facilitating access to surgery and optimising control of symptoms may improve quality of life in this group of children.
Investigations on the relationship between sweet taste perception and body mass index (BMI) have been inconclusive. Here, we report a longitudinal analysis using a genetically informative sample of 1,576 adolescent Australian twins to explore the relationship between BMI and sweet taste. First, we estimated the phenotypic correlations between perception scores for four different sweet compounds (glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame) and BMI. Then, we computed the association between adolescent taste perception and BMI in early adulthood (reported 9 years later). Finally, we used twin modeling and polygenic risk prediction analysis to investigate the genetic overlap between BMI and sweet taste perception. Our findings revealed that BMI in early adulthood was significantly associated with each of the sweet perception scores, with the strongest correlation observed in aspartame with r = 0.09 (p = .007). However, only limited evidence of association was observed between sweet taste perception and BMI that was measured at the same time (in adolescence), with the strongest evidence of association observed for glucose with a correlation coefficient of r = 0.06 (p = .029) and for aspartame with r = 0.06 (p = .035). We found a significant (p < .05) genetic correlation between glucose and NHDC perception and BMI. Our analyses suggest that sweet taste perception in adolescence can be a potential indicator of BMI in early adulthood. This association is further supported by evidence of genetic overlap between the traits, suggesting that some BMI genes may be acting through biological pathways of taste perception.
Whether supplemental Ca has similar effects to dietary Ca on vascular and bone markers is unknown. The present trial investigated the feasibility of applying dietary and supplemental interventions in a randomised-controlled trial (RCT) aiming to estimate the effect of supplemental Ca as compared with dietary Ca on vascular and bone markers in postmenopausal women. In total, thirteen participants were randomised to a Ca supplement group (CaSuppl) (750 mg Ca from CaCO3+450 mg Ca from food+20 µg vitamin D supplement) or a Ca diet group (CaDiet) (1200 mg Ca from food+10 µg vitamin D supplement). Participants were instructed on Ca consumption targets at baseline. Monthly telephone follow-ups were conducted to assess adherence to interventions (±20 % of target total Ca) using the multiple-pass 24-h recall method and reported pill count. Measurements of arterial stiffness, peripheral blood pressure and body composition were performed at baseline and after 6 and 12 months in all participants who completed the trial (n 9). Blood and serum biomarkers were measured at baseline and at 12 months. Both groups were compliant to trial interventions (±20 % of target total Ca intake; pill count ≥80 %). CaSuppl participants maintained a significantly lower average dietary Ca intake compared with CaDiet participants throughout the trial (453 (sd 187) mg/d v. 1241 (sd 319) mg/d; P<0·001). There were no significant differences in selected vascular outcomes between intervention groups over time. Our pilot trial demonstrated the feasibility of conducting a large-scale RCT to estimate the differential effects of supplemental and dietary Ca on vascular and bone health markers in healthy postmenopausal women.
The pea leaf weevil, Sitona lineatus (Linnaeus) (Coleoptera: Curculionidae), is an important pest of field peas, Pisum sativum Linnaeus (Fabaceae), and faba beans, Vicia faba Linnaeus (Fabaceae), that has recently become established in the Prairie Provinces of Canada. Male pea leaf weevils produce an aggregation pheromone, 4-methyl-3,5-heptanedione, in the spring when overwintered weevils migrate to fields to feed and mate. The current study tests the attractiveness of the aggregation pheromone with and without synthetic bean volatiles to pea leaf weevils in the spring and in the fall when weevils seek perennial legumes to feed and overwinter. Modified Leggett traps similar to those used in Europe did not retain weevils in this study. Aggregation pheromone-baited pitfall traps caught male and female weevils in the spring and fall. Weevils were not attracted to traps baited with three bean volatiles, (Z)-3-hexen-1-yl acetate, (Z)-3-hexen-1-ol, and linalool. Bean volatiles did enhance response to pheromone, but only in the fall. Weevils were captured in most semiochemical-baited traps in a 1:1 sex ratio, but female-biased catch in control traps might indicate greater activity of females in the trap vicinity. This study lays the groundwork for semiochemical-based monitoring to detect pea leaf weevil spread in the Prairie Provinces.
Sublingual immunotherapy in patients with allergic rhinitis sensitised to house dust mites is safe, but its efficacy is controversial and sublingual immunotherapy with Blomia tropicalis has not yet been studied. This study sought to evaluate the efficacy of sublingual immunotherapy with house dust mite extract in children and adults with house dust mite allergic rhinitis over a period of two years.
A prospective observational study was conducted of children and adults diagnosed with house dust mite allergic rhinitis who were treated with sublingual immunotherapy from 2008 to 2012. Total Nasal Symptom Scores, Mini Rhinoconjunctivitis Quality of Life scores and medication usage scores were assessed prospectively.
Thirty-nine patients, comprising 24 children and 15 adults, were studied. Total Nasal Symptom Scores and Mini Rhinoconjunctivitis Quality of Life scores dropped significantly at three months into therapy, and continued to improve. Medication usage scores improved at one year into immunotherapy.
Sublingual immunotherapy with house dust mite extracts, including B tropicalis, is efficacious as a treatment for patients with house dust mite allergic rhinitis.
Although the registration of a robot is crucial in order to identify its pose with respect to a tracking system, there is no reported solution to address this issue for a hybrid robot. Different from classical registration, the registration of a hybrid robot requires the need to solve an equation with three unknowns where two of these unknowns are coupled together. This property makes it difficult to obtain a closed-form solution. This paper is a first attempt to solve the registration of a hybrid robot. The Degradation-Kronecker (D-K) method is proposed as an optimal closed-form solution for the registration of a hybrid robot in this paper. Since closed-form methods generally suffer from limited accuracy, a purely nonlinear (PN) method is proposed to complement the D-K method. With simulation and experiment results, it has been found that both methods are robust. The PN method is more accurate but slower as compared to the D-K method. The fast computation property of the D-K method makes it appropriate to be applied in real-time circumstances, while the PN method is suitable to be applied where good accuracy is preferred.
Mn-doped CeO2 electrolytes formulated as Ce1-xMnxO2-x (0.05 ≤ x ≤ 0.25) were prepared via soft chemical technique which involved co-precipitation of Mn2+ and Ce4+ using oxalic acid as the precipitant. The optimized pH for a stable incorporation of Mn dopant into ceria was found to be pH = 10. The solubility limit of MnO in the CeO2 fluorite lattice structure was suggested to be x = 0.20. The phase composition, morphology properties and elemental analysis of the oxalate and derived-powder was characterized using X-ray diffraction, SEM and X-ray fluorescence (XRF) respectively. The electrical conductivity of sintered samples of Mn-doped CeO2 ceramics were investigated in air using AC impedance spectroscopy. The bulk conductivities of the Mn-doped CeO2 ceramics sintered at 1200 °C at a test temperature of 800 °C were determined to be 4.223 x 10-4 ohm-1 cm-1 for Mn content x = 0.10 with activation energy, Ea = 0.88 eV.
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.