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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
Invasive winter annual grass infestations on rangeland accumulate large quantities of litter on the soil surface, as plants senesce yearly and decompose slowly. It has been speculated that winter annual grass litter can adsorb soil-active herbicides and reduce overall performance. Three experiments were conducted from 2017 to 2018 at the Colorado State University Weed Research Laboratory to evaluate interception and subsequent desorption of herbicides applied to litter from three invasive winter annual grass species with simulated rainfall. Imazapic, rimsulfuron, and indaziflam were applied to medusahead [Taeniatherum caput-medusae (L.) Nevski], ventenata [Ventenata dubia (Leers) Coss.], and downy brome (Bromus tectorum L.) litter at two amounts (equivalent to 1,300 and 2,600 kg ha−1). Rainfall was simulated at 3, 6, 12, and 24 mm at 0, 1, and 7 d after herbicide application. Herbicide concentration from the collected rainfall was measured using liquid chromatography–tandem mass spectrometry. At 2,600 kg ha−1, B. tectorum herbicide interception was 84.3%, while V. dubia and T. caput-medusae averaged 76% herbicide interception. There were no differences in desorption among the three litter types. Simulated rainfall at 0 d after application recovered 100% of the intercepted rimsulfuron and imazapic from B. tectorum litter, while recovery decreased to 65% with rainfall at 1 or 7 d after application. Only 54% of indaziflam could be recovered at 0 d, and recovery decreased to 33% when rainfall was applied at 1 or 7 d after application. Applying soil-active herbicides before forecasted rain or tank mixing with a POST herbicide to provide initial control could potentially increase the amount of herbicide reaching the soil and provide more consistent invasive winter annual grass control.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Stripe domains in ferroelectric thin films form in order to minimize the total energy of the film. It has been known for some time that a stable configuration is reached when the decrease in elastic energy from domain formation is balanced by the energetic costs of domain wall formation, local elastic strains in the substrate, and internal electric field formation from domain polarizations. The size and strain of each domain is determined by the lattice mismatch and the energetic costs of interface formation. Recent piezoelectric force microscopy measurements have shown that BiFeO3 (BFO) films on SrRuO3/SrTiO3 (001) substrates form striped polarization domains. Since the details of the local structure and polarization cannot be measured at the same time with conventional techniques, we have used synchrotron x-ray microdiffraction to study these effects. Probing only a few domains at a time with the submicron x-ray spot resulted in a diffraction pattern near the substrate (103) reflection consisting of several BFO peaks. We have unambiguously assigned these peaks to individual structural variants. Based on these results, we propose a physical model that includes the striped domains. The structural variants within the stripes are similar to those predicted by striped patterns in rhombohedral films which minimize elastic energy. The local piezoelectric properties were measured using time-resolved microdiffraction in order to examine the role of the striped domains in the linear responses of the film. The out of plane piezoelectric coefficient d33 was approximately 50 pm/V and the piezoelectric strain was proportional to electric field was up to 0.55%, the maximum strain we have measured. The projection of the in-plane piezoelectric coefficients onto the reciprocal space maps for different structural variants had vastly different values due to the differences in orientation of the domains.
Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.
Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention.
Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity.
Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA.
DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.
To evaluate the sensitivity and specificity of the modified Evans blue dye test compared to the fibre-optic endoscopic evaluation of swallowing to detect aspiration in tracheostomised patients.
This observational accuracy study included 17 patients hospitalised for respiratory complications, subjected to prolonged intubation, and for this reason, tracheostomised.
Mean patient age was 60.2 ± 21.0 years. Aspiration was identified in 10 patients when assessed by fibre-optic endoscopic evaluation of swallowing; of these, 1 had aspiration when evaluated by modified Evans blue dye test. The dye test had a sensitivity of 10.0 per cent and specificity of 100.0 per cent for detecting aspiration. Fibre-optic endoscopic evaluation of swallowing revealed no statistically significant associations between aspiration presence and: speech and language therapy duration, intubation time, or tracheostomy plus mechanical ventilation duration.
The modified Evans blue dye test is simple and inexpensive, and does not require prior knowledge in endoscopy; it may be used as an initial screening test in all tracheostomised patients for evaluating aspiration. However, fibre-optic endoscopic evaluation of swallowing should be used for a more comprehensive diagnosis of tracheostomy patients, especially for those at high risk for aspiration.
Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
Parametrically forced gravity waves can give rise to high-velocity surface jets via the wave-depression cavity implosion. The present results have been obtained in circular cylindrical containers of 10 and 15 cm in diameter (Bond number of order
) in the large fluid depth limit. First, the phase diagrams of instability threshold and wave breaking conditions are determined for the working fluid used, here water with 1 % detergent added. The collapse of the wave-depression cavity is found to be self-similar. The exponent
of the variation of the cavity radius
, in the form
, is close to 0.5, indicative of inertial collapse, followed by a viscous cut-off of
. This supports a Froude number scaling of the surface jet velocity caused by cavity collapse. The dimensionless jet velocity scales with the cavity depth that is shown to be proportional to the last stable wave amplitude. It can be expressed by a power law or in terms of finite time singularity related to a singular wave amplitude that sets the transition from a non-pinching to pinch-off cavity collapse scenario. In terms of forcing amplitude, cavity collapse and jetting are found to occur in bands of events of non-pinching and pinching of a bubble at the cavity base. At large forcing amplitudes, incomplete cavity collapse and splashing can occur and, at even larger forcing amplitudes, wave growth is again stable up to the singular wave amplitude. When the cavity is formed, an impulse model shows the importance of the singular cavity diameter that determines the strength of the impulse.
Ten new species of Trypetheliaceae are described: Astrothelium bullatothallinum from Venezuela, which is close to A. aeneum but differs by the bullate thallus with a thick cortex, intermixed in a mosaic with the prothallus; A. cayennense from French Guiana, which is similar to A. flavomegaspermum but with a yellow pigment in the pseudostroma near the ostioles; A. diaphanocorticatum from Papua New Guinea, which has a bullate thallus with a thick hyaline cortex and 3-septate ascospores of 25–28×10–12 μm; A. macroeustomum from French Guiana, with joint lateral ostioles, UV+ yellow ostiolar region and 5-septate ascospores of 50–55×12–17 μm; A. minicecidiogenum from Costa Rica, with muriform ascospores of 70–90×20–25 μm, without pseudostromata, with solitary ascomata, lateral ostioles and an inspersed hamathecium; A. palaeoexostemmatis from Thailand, which is similar to A. exostemmatis but with larger, I+ blue ascospores; A. quasimamillanum from Brazil, with muriform ascospores of 30–33×9·5–10·5 μm, without pseudostromata, with solitary ascomata, lateral ostioles and an inspersed hamathecium; A. studerae from Brazil, with astrothelioid ascomata, lichexanthone only in the pseudostromata, 3-septate ascospores of 21·5–23·0×6·5–7·5 μm; A. tanianum from Malaysia, with a bullate thallus, solitary ascomata, covered by the thallus, (9–)11(–15)-septate ascospores, 75–100×20–22 μm; and Pseudopyrenula miniflavida from Brazil, with a yellow-inspersed hamathecium, the inspersion dissolving in KOH without colour change, and 3-septate ascospores, 15–17×5·5–6·5 μm. The unusually thick, hyaline cortical layer of the thallus of Astrothelium diaphanocorticatum, through which the individual algal cells are clearly visible, is discussed. Furthermore, 30 species are reported from 34 countries in which they had previously been unrecorded; one (Astrothelium inspersaeneum) is from a new continent, Asia.
Three new species of the Neotropical genus Barbacenia (Velloziaceae, Pandanales) from Tocantins, Brazil, are described and illustrated, based on morphology and leaf anatomy. The known species richness of the genus is mapped within the countries of South America and the states of Brazil.
The Roosevelt–Rondon Expedition marmoset Mico marcai was first collected in 1914 and all information on this primate previously came from three skins brought back by this expedition. As a result, M. marcai is categorized as Data Deficient on the IUCN Red List. As the presumed range of M. marcai lies on the path of the advancing arc of deforestation in Brazil, the collection of relevant data to assess the conservation status of this Amazonian species is of some urgency. Here we present the first field data on the distribution and population size of, and threats to, M. marcai, to reassess the species’ conservation status. During 2012–2015 we surveyed the species in the Marmelos–Aripuanã interfluve, and estimated its density using distance sampling. We also used spatial predictive modelling to estimate forest loss within the species range under two deforestation scenarios. We found the marmoset in 13 localities and estimated its extent of occurrence to be 31,073 km2. We estimated the species’ density to be 8.31 individuals/km2 and extrapolated this to estimate a total population of 258,218 individuals (CI 150,705–441,860). Under a business-as-usual deforestation scenario, c. 10,000 km2 of forest, comprising 33% of the species’ range, would be lost in three marmoset generations (c. 18 years), and we, therefore, recommend that M. marcai be categorized as Vulnerable on the IUCN Red List based on criterion A3c. Other Amazonian marmosets require similar reassessment as their ranges also fall in the path of the arc of deforestation.
Atom probe tomography (APT) is rising in influence across many parts of materials science and engineering thanks to its unique combination of highly sensitive composition measurement and three-dimensional microstructural characterization. In this invited article, we have selected a few recent applications that showcase the unique capacity of APT to measure the local composition at structural defects. Whether we consider dislocations, stacking faults, or grain boundary, the detailed compositional measurements tend to indicate specific partitioning behaviors for the different solutes in both complex engineering and model alloys we investigated.
The influence of the concentration of carbon black nanoparticles on the mechanical behavior of a structural adhesive was studied to evaluate and understand the stiffness, strength, and deformation behavior of a reinforced epoxy adhesive. Two carbon black nanoparticles with different dielectric properties and sizes (Monarch® 120 and Vulcan® XC72R) were studied. A bi-component structural epoxy adhesive was selected. Specimens with different concentrations of carbon black were manufactured (0, 5, 10, and 20% on volume of resin) for each type of nanoparticle. The specimens were cured in a hydraulic hot-plates press machine. The mechanical behavior of the adhesives was found not to vary significantly as a function of carbon black nanoparticles amount. A scanning electron microscopy analysis was performed to evaluate the fracture surface. The fracture surfaces of specimens were correlated with the mechanical response obtained through tensile tests.
Depression is associated with increased mortality, however, little is known about its variation by ethnicity.
We conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007–2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures.
Data from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45–2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53–0.74) (Black Caribbean), 0.53(95% CI 0.39–0.72) (Black African) and 0.69(95% CI 0.52–0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68–2.24) and aHR:1.18 (95% CI 1.01–1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58–0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression.
Although individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.
Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms.
In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)].
Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS.
Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes.
Necrotising enterocolitis (NEC) is a devastating disease that typically affects formula-fed premature infants, suggesting that dietary components may influence disease pathogenesis. TAG are the major fat components of infant formula, and their digestion requires pancreatic lipases, which may be naturally deficient in premature neonates. We hypothesise that NEC develops partly from the accumulation of incompletely digested long-chain TAG-containing unsaturated fatty acids within the intestinal epithelial cells, leading to oxidative stress and enterocyte damage. We further hypothesise that the administration of a formula that contains reduced TAG (‘pre-digested fat’) that do not require lipase action may reduce NEC severity. To test these hypotheses, we induced NEC in neonatal mice using three different fat formulations, namely ‘standard fat’, ‘pre-digested fat’ or ‘very low fat’, and determined that mice fed ‘standard fat’ developed severe NEC, which was significantly reduced in mice fed ‘pre-digested fat’ or ‘very low fat’. The expression level of the critical fat-digesting enzyme carboxyl ester lipase was significantly lower in the newborn compared with older pups, leading to impaired fat digestion. The accumulation of mal-digested fat resulted in the significant accumulation of fat droplets within the intestinal epithelium of the distal ileum, resulting in the generation of reactive oxygen species and intestinal inflammation. Strikingly, these changes were prevented in pups fed ‘pre-digested fat’ or ‘very low fat’ formulas. These findings suggest that nutritional formula containing a pre-digested fat system may overcome the natural lipase deficiency of the premature gut, and serve as a novel approach to prevent NEC.