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Adults with ADHD describe self-medicating with cannabis. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from trials. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms. From 17.07.14-18.06.15, 30 participants were randomly assigned to the active (n=15) or placebo (n=15) group. For the primary outcome, no significant difference was found in the intent-to-treat analysis although the overall pattern of scores was such that the active group usually had scores that were better than the placebo group (Est=-0.17,95%CI-0.40-0.07, p=0.16, n=15/11 active/placebo). For secondary outcomes Sativex was associated with a nominally significant improvement in hyperactivity/impulsivity (p=0.03) and a cognitive measure of inhibition (p=0.05), and a trend towards improvement for inattention (p=0.10) and EL (p=0.11). Per-protocol effects were higher. Results did not meet significance following adjustment for multiple testing. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problems) adverse event in the placebo group. Adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. While not definitive, this study provides preliminary evidence supporting the self-medication theory of cannabis use in ADHD and the need for further studies of the endocannabinoid system in ADHD.
During this work-RC was a Ph.D. student funded by a grant to PA from Vifor Pharma. PA received funds (consultancy/sponsored talks/research/education) from Shire, Lilly, Novartis, Janssen, PCMScientific, Vifor Pharma, QBTech. Sativex was free from GW Pharm
We describe an adolescent with Streptococcus pneumoniae meningitis and symptomatic high-grade, second-degree atrioventricular block requiring permanent pacemaker placement. It is difficult to ascertain if these two diagnoses were independent or had a causal relationship though ongoing symptoms were not present prior to the infection. Because of this uncertainty, awareness that rhythm disturbances can be cardiac in origin but also secondary to other aetiologies, such as infection, is warranted.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate.
Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.
Non-tuberculous mycobacterium encephalitis is rare. Since 2013, a global outbreak of Mycobacterium chimaera infection has been attributed to point-source contamination of heater cooler units used in cardiac surgery. Disseminated M. chimaera infection has presented many unique challenges, including non-specific clinical presentations with delays in diagnosis, and a high mortality rate among predominantly immunocompetent adults. Here, we describe three patients with fatal disseminated Mycobacterium chimaera infection showing initially non-specific, progressively worsening neurocognitive decline, including confusion, delirium, depression and apathy. Autopsy revealed widespread granulomatous encephalitis of the cerebrum, brain stem and spinal cord, along with granulomatous chorioretinitis. Cerebral involvement and differentiation between mycobacterial granulomas and microangiopathic changes can be assessed best on MRI with contrast enhancement. The prognosis of M. chimaera encephalitis appears to be very poor, but might be improved by increased awareness of this new syndrome and timely antimicrobial treatment.
This presentation will enable the learner to:
1. Describe the clinical, radiological and neuropathological findings of Mycobacterium chimaera encephalitis
2. Be aware of this rare form of encephalitis, and explain its diagnosis, prognosis and management
We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.
Describe the epidemiological and molecular characteristics of an outbreak of Klebsiella pneumoniae carbapenemase (KPC)–producing organisms and the novel use of a cohorting unit for its control.
A 566-room academic teaching facility in Milwaukee, Wisconsin.
Solid-organ transplant recipients.
Infection control bundles were used throughout the time of observation. All KPC cases were intermittently housed in a cohorting unit with dedicated nurses and nursing aids. The rooms used in the cohorting unit had anterooms where clean supplies and linens were placed. Spread of KPC-producing organisms was determined using rectal surveillance cultures on admission and weekly thereafter among all consecutive patients admitted to the involved units. KPC-positive strains underwent pulsed-field gel electrophoresis and whole-genome sequencing.
A total of 8 KPC cases (5 identified by surveillance) were identified from April 2016 to April 2017. After the index patient, 3 patients acquired KPC-producing organisms despite implementation of an infection control bundle. This prompted the use of a cohorting unit, which immediately halted transmission, and the single remaining KPC case was transferred out of the cohorting unit. However, additional KPC cases were identified within 2 months. Once the cohorting unit was reopened, no additional KPC cases occurred. The KPC-positive species identified during this outbreak included Klebsiella pneumoniae, Enterobacter cloacae complex, and Escherichia coli. blaKPC was identified on at least 2 plasmid backbones.
A complex KPC outbreak involving both clonal and plasmid-mediated dissemination was controlled using weekly surveillances and a cohorting unit.
To better understand barriers and facilitators that contribute to antibiotic overuse in long-term care and to use this information to inform an evidence and theory-informed program.
Information on barriers and facilitators associated with the assessment and management of urinary tract infections were identified from a mixed-methods survey and from focus groups with stakeholders working in long-term care. Each barrier or facilitator was mapped to corresponding determinants of behavior change, as described by the theoretical domains framework (TDF). The Rx for Change database was used to identify strategies to address the key determinants of behavior change.
In total, 19 distinct barriers and facilitators were mapped to 8 domains from the TDF: knowledge, skills, environmental context and resources, professional role or identity, beliefs about consequences, social influences, emotions, and reinforcements. The assessment of barriers and facilitators informed the need for a multifaceted approach with the inclusion of strategies (1) to establish buy-in for the changes; (2) to align organizational policies and procedures; (3) to provide education and ongoing coaching support to staff; (4) to provide information and education to residents and families; (5) to establish process surveillance with feedback to staff; and (6) to deliver reminders.
The use of a stepped approach was valuable to ensure that locally relevant barriers and facilitators to practice change were addressed in the development of a regional program to help long-term care facilities minimize antibiotic prescribing for asymptomatic bacteriuria. This stepped approach provides considerable opportunity to advance the design and impact of antimicrobial stewardship programs.
J. F. Cooper, NASA Goddard Space Flight Center Greenbelt, Maryland, USA,
R. E. Johnson, University of Virginia Charlottesville, Virginia, USA,
P. Kollmann, Johns Hopkins University Applied Physics Laboratory Laurel, Maryland, USA,
E. Roussos, Max Planck Institute for Solar System Studies Göttingen, GERMANY,
E. C. Sittler, NASA Goddard Space Flight Center Greenbelt, Maryland, USA
Ring systems around magnetized planets are expected to have varied interactions with the magnetic fields, hot plasma, and energetic particles of the associated magnetospheres. In our solar system all the giant planets, Jupiter to Neptune, have magnetospheres with embedded rings. Each ring system and its associated moons have strong interactions with their radiation environments (the most intense of which is at Jupiter). Such interactions both erode diffuse rings (such as the E ring of Saturn) and supply plasma and energetic particles to the magnetosphere and its radiation belts. Compositional and structural measurements of rings are enabled by these interactions, such as the information obtained by detection of the secondary neutron and gamma-ray emissions produced by galactic cosmic ray (GCR) interactions with the rings. It is also notable that Earth has both a magnetosphere with radiation belts, and an artificial ring system of satellites and debris, that continuously interact. Konradi (1988) even projected that the high energy trapped protons of the inner Van Allen Belt should now be experiencing significant depletion by this interaction, and we will later discuss the possible evidence for this. Magnetized exoplanets with rings would have similar interactions.
The ring systems of Jupiter and Saturn have been explored by multiple spacecraft. The Jovian ring environment was first explored in situ in 1974 by Pioneer 11, which subsequently flew under Saturn's main rings in 1979. After passing through the Saturn ring plane near the G ring in 1981, Voyager 2 encountered Uranus in 1986 and then Neptune in 1989, but in neither case were the rings and arcs of these two ice giant planets traversed. The Galileo Probe passed across the Jovian ring in December 1995 en route to the first direct penetration into Jupiter's atmosphere. The Cassini Orbiter crossed over the Saturn A and B rings in mid-2004 (Figure 14.1) as part of the Saturn Orbital Insertion (SOI). Cassini will again traverse the main rings during its Grand Finale orbit phase many times, crossing the ring plane just inwards of the D ring, prior to final atmospheric entry in 2017. With the exception of the Cassini Plasma Spectrometer (CAPS) instrument, turned off in 2012 due to electrical problems, Cassini will continue to operate through the final observations.
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.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
Treatment of medical patients with the inflammatory cytokine, interferon-α (IFN-α), is frequently associated with the development of clinical depressive symptomatology. Several important biological correlates of the effect of IFN-α on mood have been described, but the neuropsychological changes associated with IFN-α treatment are largely unexplored. The aim of the present preliminary study was to assess the effect of IFN-α on measures of emotional processing.
We measured changes in emotional processing over 6–8 weeks in 17 patients receiving IFN-α as part of their treatment for hepatitis C virus infection. Emotional processing tasks included those which have previously been shown to be sensitive to the effects of depression and antidepressant treatment, namely facial expression recognition, emotional categorisation and the dot probe attentional task.
Following IFN-α, patients were more accurate at detecting facial expressions of disgust; they also showed diminished attentional vigilance to happy faces. IFN-α produced the expected increases in scores on depression rating scales, but there was no correlation between these scores and the changes in emotional processing.
Our preliminary findings suggest that IFN-α treatment produces negative biases in emotional processing, and this effect is not simply a consequence of depression. It is possible that increased recognition of disgust may represent a neuropsychological marker of depressive disorders related to inflammation.
The Square Kilometre Array will be an amazing instrument for pulsar astronomy. While the full SKA will be sensitive enough to detect all pulsars in the Galaxy visible from Earth, already with SKA1, pulsar searches will discover enough pulsars to increase the currently known population by a factor of four, no doubt including a range of amazing unknown sources. Real time processing is needed to deal with the 60 PB of pulsar search data collected per day, using a signal processing pipeline required to perform more than 10 POps. Here we present the suggested design of the pulsar search engine for the SKA and discuss challenges and solutions to the pulsar search venture.
During puberty young people undergo significant hormonal changes which affect metabolism and, subsequently, health. Evidence suggests there is a period of transient pubertal insulin resistance, with this effect greater in girls than boys. However, the response to everyday high and low glycaemic index (GI) meals remains unknown. Following ethical approval, forty adolescents consumed a high GI or low GI breakfast, in a randomised cross-over design. Capillary blood samples were taken during a 2-h postprandial period, examining the glycaemic and insulinaemic responses. Maturity offset and homoeostatic model assessment (HOMA) were also calculated. The glycaemic response to the breakfasts was similar between boys and girls, as shown by similar peak blood glucose concentrations and incremental AUC (IAUC) following both high and low GI breakfasts (all P>0·05). Girls exhibited a higher peak plasma insulin concentration 30 min post-breakfast following both high GI (P=0·043, g=0·69) and low GI (P=0·010, g=0·84) breakfasts, as well as a greater IAUC following high GI (P=0·041, g=0·66) and low GI (P=0·041, g=0·66) breakfasts. HOMA was positively correlated with the insulinaemic responses (all P<0·0005) and maturity offset (P=0·037). The findings of the present study suggest that pubertal insulin resistance affects the postprandial insulinaemic responses to both high and low GI meals. Specifically, girls exhibit a greater insulinaemic response than boys to both meals, despite similar glycaemic responses. This study is the first to report the glycaemic and insulinaemic responses to everyday meals in boys and girls, supporting the recommendation for young people to base their diet on low GI carbohydrates.