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Background: As the second leading cause of years lived with disability in the world, and the first in people under 50, migraine represents a major burden to healthcare systems. This study examined treatment patterns and healthcare resource utilization (HRU) in patients with migraine using real-world data from Alberta. Methods: This was a retrospective cohort study of patients with ≥1 ICD-9-CM/ICD-10-CA code for migraine or ≥1 prescription for a triptan from April 1st, 2012 to March 31st, 2018. Descriptive statistics were used to characterize the study outcomes. Results: The incidence of migraine exceeded 1,000 cases per 100,000 person-years over the study period. The mean age of the cohort (n=199,931) was 40.0, and 72.3% were women. Migraine-related HRU accounted for 3%-10% of all HRU across endpoints (e.g., ED visits, hospitalization, physician visits). One-third of the cohort were prescribed acute medications (non-steroidal anti-inflammatories, triptans or other (including opioids)), whereas fewer than one-fifth were prescribed at least one migraine preventive such as tricyclic anti-depressants (proportion: 15%), anti-convulsants (13%), beta-blockers (7%), or neurotoxins (4%). Conclusions: The low medication prescription rates and high HRU indicates the potential unmet need and high disability in patients with migraine. The impact of migraine treatment patterns on HRU is an avenue for future research.
The intestinal microbiota has been indicated to have a role in the pathophysiology of AN.
Objectives
Aim of this study was to analyze fecal microbiome profiles of AN women before and after weight restoration and to combine them with fecal metabolomic profiles according to a multi-omics approach.
Methods
The gut microbiome and fecal metabolites were characterized in 21 underweight AN women and after weight restoration and compared with those of 20 healthy women. Microbiome data were correlated with the relevant fecal metabolites.
Results
AN subjects showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at different order levels in both the underweight and weight-restored condition compared to healthy women. The untargeted metabolomic procedure allowed the characterization of 224 metabolites involved in energy, lipid and amino acid metabolism. A genetic algorithm identified 49 relevant metabolites. The relationships among these fecal metabolites and bacteria genera showed structures of different complexity in the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acute phase of AN than in the weight-restored phase or normal controls. Finally, in acute AN 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome.
Conclusions
Our results provide a picture of the connections between gut bacteria and fecal metabolites in both the acute phase of AN and after short-term weight restoration. Further studies should aim to investigate the significance of gut microbiome perturbations in development and treatment of AN.
Bipolar disorder (BD), along with schizophrenia, is one of the most severe psychiatric conditions and is correlated with attentional deficits and emotion dysregulation. Bipolar patients appear to be highly sensitive to the presence of emotional distractors. Yet, no study has investigated whether perceptual load modulates the interference of emotionally distracting information. Our main goal was to test whether bipolar patients are more sensitive to task-irrelevant emotional stimulus, even when the task demands a high amount of attentional resources.
Fourteen participants with BD I or BD II and 14 controls, age- and gender-matched, performed a target-letter discrimination task with emotional task-irrelevant stimulus (angry, happy and neutral facial expressions). Target-letters were presented among five distractor-letters, which could be the same (low perceptual load) or different (high perceptual load). Participants should discriminate the target-letter and ignore the facial expression. Response time and accuracy rate were analyzed.
Results
showed a greater interference of facial stimuli at high load than low load, confirming the effectiveness of perceptual load manipulation. More importantly, patients tarried significantly longer at high load. This is consistent with deficits in control of attention, showing that bipolar patients are more prone to distraction by task-irrelevant stimulus only when the task is more demanding. Moreover, for bipolar patients neutral and angry faces resulted in a higher interference with the task (longer response time), compared to controls, suggesting an attentional bias for neutral and threating social cues. Nevertheless, a more detailed investigation regarding the attentional impairments in social context in BD is needed.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.
Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later.
Design, setting, participants, and measurements:
We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale–Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later.
Results:
Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen’s d ≤ −0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = −0.8, 95% confidence interval: −1.6, −0.1, p = 0.03) independent of self-reported activity restriction and other key factors.
Conclusions:
These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).
Objectives: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer’s disease (AD) and other neurological disorders, including Huntington’s disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. Methods: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes – across-trial novel intrusions and across/within trial repeated intrusions – in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. Results: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. Conclusions: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.
Objectives: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington’s disease [HD]). Methods: We compared the performance of individuals with Alzheimer’s disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Results: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Conclusions: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833–841)
The problem of pressure driven infernal type perturbations near the plasma edge is addressed analytically for a circular limited tokamak configuration which presents an edge flattened safety factor. The plasma is separated from a metallic wall, either ideally conducting or resistive, by a vacuum region. The dispersion relation for such types of instabilities is derived and discussed for two classes of equilibrium profiles for pressure and mass density.
The baseline of East-West array of the Fleurs Synthesis Telescope (FST) has been extended from 786 metres to 1585 metres by the addition of two 13.7 metre dishes. A digital receiver has been built to accommodate the extra delay and correlation requirements, low noise FET preamplifiers have been installed on the large antennas, and a software package has been developed for processing observation data on a VAX 11/780. The FST is now capable of producing accurate wide field maps at 1415 MHz with a resolution of 20 arc seconds and a sensitivity of several milliJansky.
Novel free boundary magnetohydrodynamic equilibrium states with spontaneous three-dimensional (3-D) deformations of the plasma–vacuum interface are computed. The structures obtained look like saturated ideal external kink/peeling modes. Large edge pressure gradients yield toroidal mode number $n=1$ distortions when the edge bootstrap current is large and higher $n$ corrugations when this current is small. Linear ideal MHD stability analyses confirm the nonlinear saturated ideal kink equilibrium states produced and we can identify the Pfirsch–Schlüter current as the main linear instability driving mechanism when the edge pressure gradient is large. The dominant non-axisymmetric component of this Pfirsch–Schlüter current drives a near resonant helical parallel current density ribbon that aligns with the near vanishing magnetic shear region caused by the edge bootstrap current. This current ribbon is a manifestation of the outer mode previously found on JET (Solano 2010). We claim that the equilibrium corrugations describe structures that are commonly observed in quiescent H-mode tokamak discharges.
JET experiments have compared the efficacy of low- and high-field side ion cyclotron resonance heating (ICRH) as an actuator to deliberately minimise the sawtooth period. It is found that low-field side ICRH with low minority concentration is optimal for sawtooth control for two main reasons. Firstly, low-field side heating means that any toroidal phasing of the ICRH ($-90^{\circ }$, $+90^{\circ }$ or dipole) has a destabilising effect on the sawteeth, meaning that dipole phasing can be employed, since this is preferable due to less plasma wall interaction from Resonant Frequency (RF) sheaths. Secondly, the resonance position of the low-field side ICRH does not have to be very accurately placed to achieve sawtooth control, relaxing the requirement for real-time control of the RF frequency. These empirical observations have been confirmed by hybrid kinetic–magnetohydrodynamic modelling, and suggest that the ICRH antenna design for ITER is well positioned to provide a control actuator capable of having a significant effect on the sawtooth behaviour.
NGC 1266 is a nearby field galaxy observed as part of the ATLAS3D survey (Cappellari et al. 2011). NGC 1266 has been shown to host a compact (< 200 pc) molecular disk and a mass-loaded molecular outflow driven by the AGN (Alatalo et al. 2011). Very Long Basline Array (VLBA) observations at 1.65 GHz revealed a compact (diameter < 1.2 pc), high brightness temperature continuum source most consistent with a low-level AGN origin. The VLBA continuum source is positioned at the center of the molecular disk and may be responsible for the expulsion of molecular gas in NGC 1266. Thus, the candidate AGN-driven molecular outflow in NGC 1266 supports the picture in which AGNs do play a significant role in the quenching of star formation and ultimately the evolution of the red sequence of galaxies.
Five capture-recapture experiments with three species of the group of Anopheles punctulatus Dönitz were undertaken in four villages in Madang Province, Papua New Guinea. Females were collected in landing catches, blood-fed, marked with fluorescent powder according to time and location of capture, and released. Recaptures took place for 4–13 nights after release. A proportion of the recaptured mosquitoes was dissected for evidence of recent oviposition and gonotrophic age determination. Two models were developed to test a number of the assumptions that underlie the analysis of capture-recapture data from mosquitoes. Species abundance and numbers collected varied within and between villages, but marked mosquitoes dispersed at random within the mosquito population. No heterogeneity was found between indoor and outdoor biters of any of the three species. Survival rates were similar in all species. Significant differences were found in the duration of the oviposition cycle between species and village. This was 2·7–3·7 days for A. punctulatus, 2·4–3·2 days for A. koliensis Owen and 2·1–3·0 days for A. farauti Laveran. No differences were found in the duration of the oviposition cycle of nulliparous and parous females of A. farauti. Thus temporary pool breeders had a longer cycle than permanent pool breeders. This tended to be due to a delay in returning to feed rather than a delay in oviposition. It is concluded that differences between local environments exert a greater influence on the duration of the oviposition cycle than do species specific differences.
A community survey of dementia was conducted on a Chinese islet. A total of 221 men and 234 women in the age range of 50–92 were assessed. The Cognitive Abilities Screening Instrument (CASI), a 100-point cognitive test designed for cross-cultural studies and adapted in Chinese for individuals with little or no formal education, was administered twice by trained field workers with a retest interval of 3 to 4 weeks. In addition, all participants were assessed by physicians who did not know the CASI scores. The physicians' assessment included a complete neurological examination, plus semi-structured tests and interviews covering cognitive abilities, daily activities, depression, cerebrovascular disease, and Parkinson's disease. Dementia was diagnosed by consensus among the physicians according to the DSM-III-R criteria. Among the 455 participants, 16 cases of dementia were identified, including 13 with probable Alzheimer's disease and 1 each with vascular dementia, Parkinson's disease, and alcoholism. The rates of dementia were 0, 3·9 and 11·5% for the age groups of 50–69, 70–79 and 80–92; and 4·4, 2·0 and 0% for the education groups of 0–1, 2–6 and 7–15 years of schooling. No sex difference was found after controlling for education. The Chinese version of the CASI had an intraclass retest reliability of 0·90. Using a cut-off score of ≤ 50 for dementia, the sensitivity was 0·88 and the specificity was 0·94. The preliminary study suggests that the CASI can be used in Chinese populations with generally low education levels and that Alzheimer's disease was the most common type of dementia in this population.
The proportion of blood meals taken on humans which are infectious to mosquitoes in the Madang area, Papua New Guinea was estimated by two methods. In the first, laboratory reared Anopheles farauti were fed on individuals of all ages at village surveys. The results showed that 3·8% of people were infectious and that the mean percentage of mosquitoes which became infected by feeding on these people was 37·9%. From the average proportion of mosquitoes infected, the probability that a mosquito feeding on a human would pick up infection was 0·013±0·005. In the second approach mosquitoes were fed on identified Plasmodium falciparum, P. vivax and P. malariae gametocyte carriers. The results indicated that 46% of gametocyte carriers were infectious and that the mean probability of a mosquito becoming infected after feeding on a gametocyte carrier was 0·151±0·029. Gametocyte prevalence rates in all ages measured over 18 months in three villages averaged 3·3% P. falciparum, 4·0% P. vivax and 0·7% P. malariae, totalling 8·0±0·7%. Combining gametocyte prevalence rates with the probability of a mosquito becoming infected from a gametocyte carrier, the probability of a mosquito becoming infected following a blood meal on a member of the human population was estimated to be 0·012±0·003.
By
Simon P. S Howarth, University of Cambridge, Cambridge CB2 ZQQ, UK,
Tjun Tang, University of Cambridge, Cambridge CB2 ZQQ, UK,
Martin J. Graves, University of Cambridge, Cambridge CB2 ZQQ, UK,
Rikin Trivedi, University of Cambridge, Cambridge CB2 ZQQ, UK,
Jamie Harle, University of Cambridge, Cambridge CB2 ZQQ, UK,
Jonathan H. Gillard, University of Cambridge, Cambridge CB2 ZQQ, UK
Ultrasmall paramagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) imaging is a promising noninvasive method to identify high-risk atheromatous plaques. Iron oxide particles function as contrast-enhancing agents by creating a large dipolar magnetic field gradient that acts on the water molecules that diffuse close to the particles. Howarth reported that USPIO appeared to show a dual contrast effect with signal enhancement being seen in plaques with little inflammation and large fibrous caps. The contralateral side of symptomatic patients given USPIO were also analyzed. It was found that 95% patients showed bilateral USPIO uptake suggesting an inflammatory burden within their carotid atheroma bilaterally. Three different approaches have been adopted to make the seemly impossible task a reality: ultrashort echo times (uTE), inversion recovery on-resonance water suppression (IRON) imaging, and Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP).
We describe a new approach to deposition of Parylene N thin films. It utilizes a small scale, sonic speed, Jet Vapor DepositionTM (JVDTM) process technology in place of the conventional larger scale, slow flow, Gorham apparatus. It employs a simple but powerful strategy to promote radical polymerization: exposure of the growing film, during deposition, to a high flux of atomic hydrogen. We believe that H atoms have two effects: they clean oxygen from the substrate, and they promote crosslinking in the Parylene film by abstraction of H atoms from the Parylene ring or side groups. With “H atom assisted JVD” Parylene N deposits and adheres even on warm substrates; it has reduced index of refraction and dielectric constant.
Background. Many studies have separately reported abnormalities of frontal and temporal lobe structures in schizophrenia, but little is known of structural fronto-temporal associations in this condition. We investigated whether male patients with chronic schizophrenia would show abnormal patterns of correlation between regional brain volumes.
Methods. Structural magnetic resonance images of the brain in 42 patients were compared with 43 matched unaffected controls. We explored the pattern of association between regional brain volumes by correlational analyses, and non-parametrically tested for significance of between-group differences by randomization.
Results. The schizophrenics demonstrated significant volume deficits in several brain regions (left temporal lobe and hippocampus, right dorsolateral prefrontal cortex), and significant volume increases in the ventricular system (third ventricle and left temporal horn of the lateral ventricle). Controls demonstrated large positive correlations (r>0·4) between prefrontal and temporal lobe regions. By contrast, inter-regional correlations significantly reduced in schizophrenics included those between prefrontal, anterior cingulate and temporal regions, and between posterior cingulate and hippocampus (P<0·05). The most salient abnormality in patients was a dissociation between prefrontal and superior temporal gyrus volumes (P<0·01).
Conclusions. These results support the existence of a relative ‘fronto-temporal dissociation’ in schizophrenia which we suggest may be due to lack of mutually trophic influences during frontal and temporal lobe development.
A significant materials-based activity to develop Ti-aluminide metal matrix composites for high temperature aerospace structural applications is now underway. A review of the approaches, progress, and status of the development of continuously-reinforced Ti-aluminide metal matrix composites with matrices which contain a significant volume fraction of the ordered orthorhombic Ti2AlNb phase will be presented. The principal application considered is a gas turbine compressor rotor ring, and this influences the development approaches and properties goals. Specific development activity that will be presented includes modification and control of the matrix composition and microstructure, fiber coating treatments to control interdiffusion between the fiber and the matrix, and to improve the ability of the interface to support a mechanical load, and efforts to improve the properties of SiC monofilaments used as reinforcements. Critical issues that define the requirements for additional studies will be presented.