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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.
School attendance rates in sub-Saharan Africa are among the lowest worldwide, placing children at heightened risk for poor educational and economic outcomes. One understudied risk factor for missed schooling is household water insecurity, which is linked to depression among women and may increase children's water-fetching burden at the expense of educational activities, particularly among children of depressed caregivers. In this study conducted in rural Uganda, we assessed the association between household water insecurity and child school participation and the mediating pathways behind these associations.
We conducted a population-based, cross-sectional study of female household heads (N = 257) and their children ages 5–17 (N = 551) in the rural regions surrounding the town of Mbarara, in southwestern Uganda. We used multivariable linear regressions to estimate the association between water insecurity and missed schooling. We then assessed the extent to which the association was mediated by caregiver depression.
Among children, water insecurity had a statistically significant association with the number of missed school days (a standard deviation increase in water insecurity resulted in 0.30 more missed school days in the last week). The estimated association was partially mediated by caregiver depression. When stratified by sex, this mediating pathway remained significant for boys, but not among girls.
Water insecurity is a risk factor for missed schooling among children in rural Uganda. Caregiver depression partially mediated this relationship. Also addressing caregiver mental health in water insecure families may more fully address the needs of sub-Saharan African families and promote educational participation among youth.
Although extinction risk has been found to have a consistent negative relationship with geographic range across wide temporal and taxonomic scales, the effect has been difficult to disentangle from factors such as sampling, ecological niche, or clade. In addition, studies of extinction risk have focused on benthic invertebrates with less work on planktic taxa. We employed a global set of 1114 planktic graptolite species from the Ordovician to lower Devonian to analyze the predictive power of species’ traits and abiotic factors on extinction risk, combining general linear models (GLMs), partial least-squares regression (PLSR), and permutation tests. Factors included measures of geographic range, sampling, and graptolite-specific factors such as clade, biofacies affiliation, shallow water tolerance, and age cohorts split at the base of the Katian and Rhuddanian stages.
The percent variance in durations explained varied substantially between taxon subsets from 12% to 45%. Overall commonness, the correlated effects of geographic range and sampling, was the strongest, most consistent factor (12–30% variance explained), with clade and age cohort adding up to 18% and other factors <10%. Surprisingly, geographic range alone contributed little explanatory power (<5%). It is likely that this is a consequence of a nonlinear relationship between geographic range and extinction risk, wherein the largest reductions in extinction risk are gained from moderate expansion of small geographic ranges. Thus, even large differences in range size between graptolite species did not lead to a proportionate difference in extinction risk because of the large average ranges of these species. Finally, we emphasize that the common practice of determining the geographic range of taxa from the union of all occurrences over their duration poses a substantial risk of overestimating the geographic scope of the realized ecological niche and, thus, of further conflating sampling effects on observed duration with the biological effects of range size on extinction risk.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.
Materials and methods
Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported.
We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission.
Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.
The Wisconsin Plasma Astrophysics Laboratory (WiPAL) is a flexible user facility designed to study a range of astrophysically relevant plasma processes as well as novel geometries that mimic astrophysical systems. A multi-cusp magnetic bucket constructed from strong samarium cobalt permanent magnets now confines a
, fully ionized, magnetic-field-free plasma in a spherical geometry. Plasma parameters of
provide an ideal testbed for a range of astrophysical experiments, including self-exciting dynamos, collisionless magnetic reconnection, jet stability, stellar winds and more. This article describes the capabilities of WiPAL, along with several experiments, in both operating and planning stages, that illustrate the range of possibilities for future users.