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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.
In this work we apply high-resolution X-ray diffractometry to the study of InGaAs/GaAs multiple quantum well structures on (001) and(lll)B GaAs substrates. The samples consisted of p-i-n diodes with a multiple quantum well embedded in the i-region and were simultaneously grown on (001) and (111)B substrates by molecular beam epitaxy. For the characterization we have used symmetric and asymmetric reflections at different azimuthal positions. The interpretation of the diffraction profiles has been possible thanks to our recently developed simulation model, which allows the calculation of any reflection regardless of the substrate orientation. X-ray results about composition and thickness are very similar in the samples simultaneously grown on both orientations as expected from our specific growth conditions. The information obtained from X-ray characterization is consistent with the results of photoluminescence and photocurrent measurements within the experimental uncertainty of the techniques. In (lll)B samples, X-ray diffractometry provides structural information which cannot be easily obtained from optical characterization techniques.
Echinococcus granulosus is an important zoonotic parasite that is distributed worldwide. The EG95 vaccine was developed to assist with control of E. granulosus transmission through the parasite's livestock intermediate hosts. The vaccine is based on a recombinant antigen encoded by a gene which is a member of a multi-gene family. With the recent availability of two E. granulosus draft genomes, we sought to map the eg95 gene family to the genomes. We were unable to map unequivocally any of the eg95 gene family members which had previously been characterized by cloning and sequencing both strands of genomic DNA fragments. Our inability to map EG95-related genes to the genomes has revealed limitations in the assembled sequence data when utilized for gene family analyses. This study contrasts with the expectations expressed in often high-profile publications describing draft genomes of parasitic organisms, highlighting deficiencies in currently available genomic resources for E. granulosus and provides a cautionary note for research which seeks to utilize these genome datasets.
Functionalization of silicone rubber films with lysozyme was achieved by grafting copolymerization and its chemical activation allowing the covalent immobilization of the enzyme. The new materials were characterized by means of Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, contact angle, atomic force microscopy, and mechanical properties of films. The enzymatic activity of films was studied by a suspension of lyophilized Micrococcus lysodeikticus. The activity test was inquired at different pH and temperatures, exhibiting enzymatic activity 20 °C above the free lysozyme, and at pH = 5 where the free lysozyme did not show activity.
To determine whether antimicrobial-impregnated textiles decrease the acquisition of pathogens by healthcare provider (HCP) clothing.
We completed a 3-arm randomized controlled trial to test the efficacy of 2 types of antimicrobial-impregnated clothing compared to standard HCP clothing. Cultures were obtained from each nurse participant, the healthcare environment, and patients during each shift. The primary outcome was the change in total contamination on nurse scrubs, measured as the sum of colony-forming units (CFU) of bacteria.
PARTICIPANTS AND SETTING
Nurses working in medical and surgical ICUs in a 936-bed tertiary-care hospital.
Nurse subjects wore standard cotton-polyester surgical scrubs (control), scrubs that contained a complex element compound with a silver-alloy embedded in its fibers (Scrub 1), or scrubs impregnated with an organosilane-based quaternary ammonium and a hydrophobic fluoroacrylate copolymer emulsion (Scrub 2). Nurse participants were blinded to scrub type and randomly participated in all 3 arms during 3 consecutive 12-hour shifts in the intensive care unit.
In total, 40 nurses were enrolled and completed 3 shifts. Analyses of 2,919 cultures from the environment and 2,185 from HCP clothing showed that scrub type was not associated with a change in HCP clothing contamination (P=.70). Mean difference estimates were 0.118 for the Scrub 1 arm (95% confidence interval [CI], −0.206 to 0.441; P=.48) and 0.009 for the Scrub 2 rm (95% CI, −0.323 to 0.342; P=.96) compared to the control. HCP became newly contaminated with important pathogens during 19 of the 120 shifts (16%).
Antimicrobial-impregnated scrubs were not effective at reducing HCP contamination. However, the environment is an important source of HCP clothing contamination.
We investigate here the effect of the selection function on the metallicity distribution function (MDF) as well as on the vertical metallicity gradient by studying similar lines-of-sight using four different spectroscopic surveys (APOGEE, LAMOST, RAVE and Gaia-ESO) which have different targeting strategies and therefore different selection functions. We create mock fields for each survey using two stellar population synthesis models, GALAXIA and TRILEGAL. The effects of the selection function are studied in detail by applying the selection function to the two models and comparing the MDF as well as vertical metallicity gradients of the selected sources with that of the underlying sample. We find a negligible selection function effect on the MDF as well as on the vertical metallicity gradients for APOGEE, RAVE and LAMOST, and estimate a mean vertical metallicity gradient of -0.241±0.028 dex kpc−1.
The purpose of this paper is to describe the development and initial accomplishments of a training program of young leaders in community mental health research as part of a Latin American initiative known as RedeAmericas. RedeAmericas was one of five regional ‘Hubs’ funded by the National Institute of Mental Health (NIMH) to improve community mental health care and build mental health research capacity in low- and middle-income countries. It included investigators in six Latin American cities – Santiago, Chile; Medellín, Colombia; Rio de Janeiro, Brazil; and Córdoba, Neuquén, and Buenos Aires in Argentina – working together with a team affiliated with the Global Mental Health program at Columbia University in New York City. One component of RedeAmericas was a capacity-building effort that included an Awardee program for early career researchers in the mental health field. We review the aims of this component, how it developed, and what was learned that would be useful for future capacity-building efforts, and also comment on future prospects for maintaining this type of effort.
Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional ‘hubs’ established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs.
The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants.
Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful.
The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.
The effect on the mechanical properties at room temperature of Li and Ag additions to the Fe–Al (40 at.%)-based alloy produced by conventional casting were evaluated in this work. Alloying elements were added into a previously molted Fe–(40 at.%) aluminum-based alloy, stirred, and then cast into sand molds to directly produce tensile specimens. To determine the mechanical properties, tensile tests and hardness measurements were performed. The additions of both Ag and Li showed an increase in ductility and tensile strength of the intermetallic alloys. In addition, hardness was substantially increased with the Li addition. Lithium additions promoted a solid solution hardening, whereas 3 at.% of Ag additions promoted ductility due to a microstructural modification and to the formation of a soft Ag3Al phase. Characterization by both optical and electronic microscopy, energy dispersive spectroscopy microanalysis, and x-ray diffraction supported the mechanical characterization.
Echinococcus granulosus (sensu lato) is now recognized as an assemblage of cryptic species, which differ considerably in morphology, development, host specificity (including infectivity/pathogenicity for humans) and other aspects. One of these species, E. granulosus sensu stricto (s.s.), is now clearly identified as the principal agent causing cystic echinococcosis in humans. Previous studies of a small section of the cox1 and nadh1 genes identified two variants of E. granulosus s.s. to be present in Australia; however, no further work has been carried out to characterize the microdiversity of the parasite in its territory. We have analysed the sequence of the full length of the cox1 gene (1609 bp) from 37 isolates of E. granulosus from different hosts and geographic regions of Australia. The analysis shows that seven haplotypes of E. granulosus s.s. not previously described were found, together with five haplotypes known to be present in other parts of the world, including the haplotype EG01 which is widespread and present in all endemic regions. These data extend knowledge related to the geographical spread and host range of E. granulosus s.s. in a country such as Australia in which the parasite established around 200 years ago.
RNA polymerase III (Pol III) synthesizes small RNA molecules that are essential for cell viability. Accurate initiation of transcription by Pol III requires general transcription factor TFIIIB, which is composed of three subunits: TFIIB-related factor BRF1, TATA-binding protein and BDP1. Here we report the molecular characterization of BRF1 in Trypanosoma brucei (TbBRF1), a parasitic protozoa that shows distinctive transcription characteristics. In silico analysis allowed the detection in TbBRF1 of the three conserved domains located in the N-terminal region of all BRF1 orthologues, namely a zinc ribbon motif and two cyclin repeats. Homology modelling suggested that, similarly to other BRF1 and TFIIB proteins, the TbBRF1 cyclin repeats show the characteristic structure of five α-helices per repeat, connected by a short random-coiled linker. As expected for a transcription factor, TbBRF1 was localized in the nucleus. Knock-down of TbBRF1 by RNA interference (RNAi) showed that this protein is essential for the viability of procyclic forms of T. brucei, since ablation of TbBRF1 led to growth arrest of the parasites. Nuclear run-on and quantitative real-time PCR analyses demonstrated that transcription of all the Pol III-dependent genes analysed was reduced, at different levels, after RNAi induction.
Several studies have evaluated the short-term effects of tropical forest fragmentation on plant taxonomic diversity, while only a few have evaluated its effects on functional or phylogenetic diversity. To our knowledge no study has looked at the long-term consequences of tropical forest fragmentation on the three main components of plant diversity simultaneously: taxonomic, functional and phylogenetic diversity. We sampled the vascular flora using belt transects (50 × 4 m) in a continuous tropical semi-evergreen forest (16 transects) and in an adjacent naturally fragmented forest (fragments of 1.7-My-old semi-evergreen forest immersed in a mangrove/sedge matrix) (18 transects), and compared their taxonomic, functional and phylogenetic plant diversity. There were 36 species in the continuous forest and 28 in the fragmented forest. Continuous forest was taxonomically more diverse (25%) than the fragmented forest. All functional diversity metrics were greater (6–33%) in the continuous than in the fragmented forest. Phylogenetic diversity was 19% greater and phylogenetically more overdispersed in the continuous forest than in the fragmented forest. The results suggest that in the fragmented forest not only is taxonomic plant diversity lower, but functional and phylogenetic diversity are as well. The negative effects of forest fragmentation on plant diversity seem to be chronic.
The Vista Variables in the Vía Láctea (VVV) ESO Public Survey is an ongoing time-series, near-infrared (IR) survey of the Galactic bulge and an adjacent portion of the inner disk, covering 562 square degrees of the sky, using ESO's VISTA telescope. The survey has provided superb multi-color photometry in 5 broadband filters (Z, Y, J, H, and Ks), leading to the best map of the inner Milky Way ever obtained, particularly in the near-IR. The main part of the survey, which is focused on the variability in the Ks-band, is currently underway, with bulge fields observed between 34 and 73 times, and disk fields between 34 and 36 times. When the survey is complete, bulge (disk) fields will have been observed up to a total of 100 (60) times, providing unprecedented depth and time coverage in the near-IR. Here we provide a first overview of stellar variability in the VVV data.