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Interactions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees.
One thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire.
The total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean) = 0.92, SD = 1.44, range = 0–12) and most in Portugal (M = 19.06, SD = 17.44, range = 0–100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M = 3.30, SD = 1.26 vs. M = 2.39, SD = 1.06 on a 5-point Likert scale: 1 “completely disagree” to 5 “completely agree”). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio) = 1.21, 95%CI = 1.12–1.30 and OR = 1.18, 95%CI = 1.02–1.37).
There are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.
The influence of pharmaceutical industry (PI) on clinical practice and research in psychiatry has been considered a serious problem. Strict rules and guidelines were developed to regulate the interactions between doctors and PI. However, there is an ongoing debate whether these were thoroughly implemented in practice and internalized by physicians. The objective of our study was to assess the attitudes and behaviors of trainees in psychiatry and child & adolescent psychiatry toward PI across Europe. Methodologically, a validated questionnaire with additional items was administered to1444 trainees in 20 European countries. The minimum response rate was set at 60%. We found a high variation across countries in number of interactions between trainees and PI representatives; Portugal and Turkey had the highest number of interactions. The majority (59.76%) agreed that interactions with PI representatives have an impact on physicians’ prescribing behavior; whereas only 29.26% and 19.79% agreed interactions with PI representatives and gifts from PI have impact on their own prescribing behavior, respectively. Most of the gifts were considered appropriate by the majority, except tickets to vacation spot and social dinner at a restaurant. Of the sample, 70.76% think they have not been given sufficient training regarding how to interact with PI representatives. Only less than 20% indicated they have guidelines at institutional or national level. In conclusion, there is substantial interaction between trainees and PI across countries. The majority feel inadequately trained regarding professional interaction with PI, and believes they are immune to the influence of PI.
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.
The large scatter in Lyman-α opacity at z > 5.3 has been an ongoing mystery, prompting a flurry of numerical models. A uniform ultra-violet background has been ruled out at those redshifts, but it is unclear whether any proposed models produce sufficient inhomogeneities. In this paper we provide an update on the measurement which first highlighted the issue: Lyman-α effective optical depth along high-z quasar lines of sight. We nearly triple on the previous sample size in such a study thanks to the cooperation of the DES-VHS, SHELLQs, and SDSS collaborations as well as new reductions and spectra. We find that a uniform UVB model is ruled out at 5.1 < z < 5.3, as well as higher redshifts, which is perplexing. We provide the first such measurements at z ∼ 6. None of the numerical models we confronted to this data could reproduce the observed scatter.
Static surface shapes of a magnetic fluid volume between two plates in a non-uniform magnetic field are investigated theoretically and experimentally. Abrupt changes and hysteresis of the magnetic fluid surface shape are observed in the experiments when the current in the coil increases and decreases quasi-statically. The necessary and sufficient conditions for a local minimum of the energy functional are derived theoretically. A method to find stable/unstable surface shapes is developed. The ambiguity in the determination of the magnetic fluid surface shape at the same value of the current is shown. It is found that the experimentally observed surface shapes of the given magnetic fluid volume coincide with the shapes obtained numerically, and practically all of them satisfy the derived necessary and sufficient conditions of the minimum energy. The stability curves of the magnetic fluid bridge between the plates are determined experimentally and theoretically.
Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD.
Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations.
PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks.
We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.
Social anxiety disorder (SAD) is characterized by fear of social and performance situations. The consequence of scrutiny by others for the neural processing of performance feedback in SAD is unknown.
We used event-related functional magnetic resonance imaging to investigate brain activation to positive, negative, and uninformative performance feedback in patients diagnosed with SAD and age-, gender-, and education-matched healthy control subjects who performed a time estimation task during a social observation condition and a non-social control condition: while either being monitored or unmonitored by a body camera, subjects received performance feedback after performing a time estimation that they could not fully evaluate without external feedback.
We found that brain activation in ventral striatum (VS) and midcingulate cortex was modulated by an interaction of social context and feedback type. SAD patients showed a lack of social-context-dependent variation of feedback processing, while control participants showed an enhancement of brain responses specifically to positive feedback in VS during observation.
The present findings emphasize the importance of social-context processing in SAD by showing that scrutiny prevents appropriate reward-processing-related signatures in response to positive performances in SAD.
The main goal of this work consisted in cloning, purifying and characterizing a protein phosphatase 2C (PP2C) from promastigotes of Leishmania major. The gene was cloned and amplified by PCR using specific oligonucleotides and the recombinant protein was purified by affinity chromatography. The peak with maximal protein concentration was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and revealed a protein of 44·9 kDa with PP2C activity. This activity was dependent on divalent cations (Mg+2 and Mn+2) and was optimal at pH of 8·5, using phosphothreonine as the substrate. Sanguinarine inhibited the activity of the recombinant LmPP2C, while protein tyrosine phosphatase inhibitors had no effect. The recombinant LmPP2C was used to generate polyclonal antibodies. These antibodies recognized a protein of 44·9 kDa in different Leishmania species; the LmPP2C was localized in the flagellar pocket and the flagellum of promastigotes.
Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1β, IL-12p70 and IL-10 in human macrophages.
This study aimed at comparing data obtained from Azawak zebu colostrum with literature data. The comparison was performed by a meta-analytical approach. Colostrum samples were hand-collected after 5 h from seven Azawak cows at calving between August 27 and September 10, 2009 in the Sahel. For data from literature, 21 references were identified in the following analytical databases: PubMed, Science Direct, Google scholar, Collection from University of Liege. The references were selected according to the following two criteria: (i) only studies reported on bovine colostrum were used irrespective of breeds, and (ii) among the selected studies, those not providing complete information to allow meta-analytical calculation were excluded. Samples were analysed for immunoglobulins (IgG, IgM and IgA), lactoferrin and chemical composition (dry mater, protein, fat, lactose, ash, Ca, P, NA, K and Mg). The mean levels of IgG, IgM, dry matter, protein and fat for Azawak cows were lower (P < 0.001) than those obtained in other breeds; however, colostrum from the Azawak was higher in IgA but the difference was not significant. For lactose and ash, mean values for Azawak cows were higher (P < 0.001) than those from the literature. Contents of Ca, P, Na and Mg in Azawak bovine colostrum were significantly higher (P < 0.001) than the mean levels in form the literature data. In conclusion, the colostrum from Azawak cows appears to be lower in most immunoglobulins, in fat and in protein than the values reported in the literature, but higher in lactose and minerals. This could be an adaptation to Sahelian constraints.
Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. Leishmania promastigotes primarily infect macrophages in the host, where they transform into amastigotes and multiply. Lipophosphoglycan (LPG), the most abundant surface molecule of the parasite, is a virulence determinant that regulates the host immune response. Promastigotes are able to modulate this effect through LPG, creating a favourable environment for parasite survival, although the mechanisms underlying this modulation remain unknown. We analysed the participation of TLR2 and TLR4 in the production of cytokines and explored the possible phosphorylation of ERK and/or p38 MAP kinase signalling cascades in human macrophages stimulated with Leishmania mexicana LPG. The results show that LPG induced the production of TNF-α, IL-1β, IL-12p40, IL-12p70 and IL-10 and led to phosphorylation of ERK and p38 MAP kinase. Specific inhibitors of ERK or p38 MAP kinases and mAbs against TLR2 and TLR4 reduced cytokine production and phosphorylation of both kinases. Our results suggest that L. mexicana LPG binds TLR2 and TLR4 receptors in human macrophages, leading to ERK and MAP kinase phosphorylation and production of pro-inflammatory cytokines.
Tissue engineering principles suggest the formation of 3D scaffolds based on polymer fibers and adhesive proteins. These scaffolds aim to mimic the native extracellular matrix and thus providing a favorable environment for cell attachment and proliferation. The application of an electric field (EF) can influence the quantity and the spatial orientation/conformation of adsorbed proteins, which could lead to changes in their functions. We study the influence of alternating current (AC) EF on the adsorption of fibronectin onto poly(etherimide) (PEI) electrospun fiber materials in 3D structures and subsequent cell adhesion. The results are compared with 2D PEI material and glass surface. 3D scaffolds adsorbed a lower amount of fibronectin than 2D film or glass. Application of AC EF with a frequency of 1 Hz decreased the adsorption of fibronectin. Cell adhesion on 3D materials was reduced compared with 2D film and glass. The application of EF with frequencies between 1 and 10 Hz improved cell adhesion on both 2D and 3D materials.
EMU is a wide-field radio continuum survey planned for the new Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The primary goal of EMU is to make a deep (rms ∼ 10 μJy/beam) radio continuum survey of the entire Southern sky at 1.3 GHz, extending as far North as +30° declination, with a resolution of 10 arcsec. EMU is expected to detect and catalogue about 70 million galaxies, including typical star-forming galaxies up to z ∼ 1, powerful starbursts to even greater redshifts, and active galactic nuclei to the edge of the visible Universe. It will undoubtedly discover new classes of object. This paper defines the science goals and parameters of the survey, and describes the development of techniques necessary to maximise the science return from EMU.
Aluminum-doped zinc oxide (ZnOx:Al) films have been deposited on a moving glass substrate by a high throughput metalorganic chemical vapor deposition process at atmospheric pressure. Thin (< 250 nm) ZnOx:Al films have a poor crystalline quality, due to a small grain size and the presence of different crystallographic orientations. The crystalline quality improves with increasing film thickness (from 50 nm to 1000 nm), resulting in a lower value of resistivity (from 100 Ohm cm to 1·10-3 Ohm cm, respectively). We have investigated the variation in the films’ conductivity and transparency induced by a post-deposition exposure to a He/H2 atmospheric plasma. The resistivity of thin (< 250 nm) films is found to decreased sharply from 100 Ohm cm to about 4·10-3 Ohm cm by a short (∼ seconds) plasma exposure, while the resistivity of thicker films remains unaffected.
High quality single crystal boron-doped diamond films are deposited in a microwave plasma-assisted CVD reactor with feedgas mixtures including hydrogen, methane, diborane, and carbon dioxide at reactor pressures of 160 Torr. The effect of diborane levels and other growth parameters on the incorporated boron levels are investigated, and the doping efficiency is calculated over a wide range of boron concentrations. The boron level is investigated using infrared absorption, and compared to SIMS measurements, and defects are shown to affect the doping uniformity.
We report on life course stress determinants of overweight in children, using data from the longitudinal follow-up of the nested case–control arm of the SAGE (study of asthma genes and the environment) birth cohort in Manitoba, Canada. Waist and hip measurements were obtained during a clinic visit at age 9–11 years. Multiple linear regression was conducted to determine the relationship between the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal distress and stress reactivity in children (cortisol, cortisol-DHEA [dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8–10 years. We found waist-to-hip risk at age 9–11 years to be elevated among boys and girls whose mothers had experienced distress in the postnatal period. This association varied by gender and asthma status. In healthy girls, postpartum distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01), independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio and duration of exclusive breastfeeding. Among girls with asthma, maternal smoking during pregnancy was associated with an increased waist-to-hip ratio, if the mother also experienced distress in the postpartum period (0.072, P = 0.038). Among asthmatic boys, an association between maternal distress and waist-to-hip ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to leptin and infant over-eating pathways were proposed to explain the postnatal maternal distress effects. Drawing on the theories of evolutionary biology, our findings underscore the significance of postnatal stress in disrupting hypothalamic–pituitary–adrenal axis function in infants and increasing risk for child overweight.
Certain health risks have been associated with recreational exposure to faecally polluted water. Canoeing in certain South African waters is considered to be a high risk activity with regard to schistosomiasis. gastroenteritis and possibly hepatitis. In a cross-sectional study, a serosurvey was conducted amongst canoeists to ascertain whether or not they had a higher seroprevalence to hepatitis A virus. Norwalk virus and Schistosoma spp. than non-canoeists. In comparisons between the two groups, a significant association could not be demonstrated between canoeing and antibody response to hepatitis A and Norwalk viruses (P-values for age-adjusted χ2 were 0·083 and 0·219 respectively), but a significant association could be demonstrated between canoeing and the antibody response to Schistosoma spp. (P > 0·001: age-adjusted).
Two fundamentally different types of domains were resolved in multiferroic MnWO4 by optical second harmonic generation (SHG). Hybrid-multiferroic (absolute) domains reflect the magnetic chirality coupled 1:1 to the spontaneous polarization because of the magnetic origin of the ferroelectric order. Magnetic translation (relative) domains reflect discontinuities in the progression of the magnetic spin spiral. SHG topography is the only experimental method so far allowing one to image both types of domains. The imaging procedure and the SHG contributions involved are therefore discussed in detail.