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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
This study evaluated the efficacy of a family-centered preventive intervention, the Family Check-Up (FCU), delivered as an online, eHealth model to middle school families. To increase accessibility of family-centered prevention in schools, we adapted the evidence-based FCU to an online format, with the goal of providing a model of service delivery that is feasible, given limited staffing and resources in many schools. Building on prior research, we randomly assigned participants to waitlist control (n = 105), FCU Online as a web-based intervention (n = 109), and FCU Online with coaching support (n = 108). We tested the effects of the intervention on multiple outcomes, including parental self-efficacy, child self-regulation, and child behavior, in this registered clinical trial (NCT03060291). Families engaged in the intervention at a high rate (72% completed the FCU assessment) and completed 3-month posttest assessments with good retention (94% retained). Random assignment to the FCU Online with coaching support was associated with reduced emotional problems for children (p = .003, d = −0.32) and improved parental confidence and self-efficacy (p = .018, d = 0.25) when compared with waitlist controls. Risk moderated effects: at-risk youth showed stronger effects than did those with minimal risk. The results have implications for online delivery of family-centered interventions in schools.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
To determine infection prevention and control (IPAC) practices for carbapenemase-producing Enterobacteriaceae (CPE), an emerging threat, at acute-care hospitals in Ontario, Canada.
A descriptive cross-sectional survey.
We surveyed IPAC directors and managers at all acute-care hospitals in Ontario, Canada, to gather information on IPAC practices related to CPE, including admission screening, other patient screening, environmental testing, use of precautions to prevent transmission, and outbreak management.
Of 116 acute-care hospitals, 105 (91%) responded. Admission screening included patients previously colonized or infected with CPE (n = 64, 61%), patients recently hospitalized outside of Canada (Indian subcontinent, n = 62, 59%; other countries, n = 56, 53%), and patients recently hospitalized in Canada (n = 22, 21%). Fifty-one hospitals (49%) screened patients for colonization during an outbreak. Almost all hospitals (n = 101, 96%) used precautions to prevent transmission from patients with CPE colonization or infection; most hospitals (n = 54, 53%) continued precautions indefinitely. Few hospitals (n = 19, 18%) performed environmental cultures. Eight hospitals (8%) reported at least 1 outbreak, and 6 hospitals (6%) reported transmission from sink or shower drains to patients.
Variability in practices may result from lack of evidence and challenges in updating guidelines as evidence emerges. A coordinated approach to slow the emergence of CPE should be considered in our population.
Compound heterozygotes occur when different variants at the same locus on both maternal and paternal chromosomes produce a recessive trait. Here we present the tool VarCount for the quantification of variants at the individual level. We used VarCount to characterize compound heterozygous coding variants in patients with epileptic encephalopathy and in the 1000 Genomes Project participants. The Epi4k data contains variants identified by whole exome sequencing in patients with either Lennox-Gastaut Syndrome (LGS) or infantile spasms (IS), as well as their parents. We queried the Epi4k dataset (264 trios) and the phased 1000 Genomes Project data (2504 participants) for recessive variants. To assess enrichment, transcript counts were compared between the Epi4k and 1000 Genomes Project participants using minor allele frequency (MAF) cutoffs of 0.5 and 1.0%, and including all ancestries or only probands of European ancestry. In the Epi4k participants, we found enrichment for rare, compound heterozygous variants in six genes, including three involved in neuronal growth and development – PRTG (p = 0.00086, 1% MAF, combined ancestries), TNC (p = 0.022, 1% MAF, combined ancestries) and MACF1 (p = 0.0245, 0.5% MAF, EU ancestry). Due to the total number of transcripts considered in these analyses, the enrichment detected was not significant after correction for multiple testing and higher powered or prospective studies are necessary to validate the candidacy of these genes. However, PRTG, TNC and MACF1 are potential novel recessive epilepsy genes and our results highlight that compound heterozygous variants should be considered in sporadic epilepsy.
Cascading effects of high trophic levels onto lower trophic levels have been documented in many ecosystems. Some studies also show evidence of extended trophic cascades, in which guilds dependent on lower trophic levels, but uninvolved in the trophic cascade themselves, are affected by the trophic cascade due to their dependence on lower trophic levels. Top-down effects of large mammals on plants could lead to a variety of extended trophic cascades on the many guilds dependent on plants, such as pollinators. In this study, floral-visitor and floral abundances and assemblages were quantified within a series of 1-ha manipulations of large-mammalian herbivore density in an African savanna. Top-down effects of large mammals on the composition of flowers available for floral visitors are first shown, using regressions of herbivore activity on metrics of floral and floral-visitor assemblages. An extended trophic cascade is also shown: the floral assemblage further altered the assemblage of floral visitors, according to a variety of approaches, including a structural equation modelling approach (model with an extended trophic cascade was supported over a model without, AICc weight = 0.984). Our study provides support for extended trophic cascades affecting floral visitors, suggesting that trophic cascades can have impacts throughout entire communities.
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.
Population density is often a critical factor in colonisation of trees by bark and wood-boring insects and may determine whether an exotic species is likely to establish and spread. In a manipulative field study, we investigated whether density of the attacking population of an exotic invasive woodwasp, Sirex noctilio Fabricius (Hymenoptera: Siricidae), affected survival and time-to-death of a favoured host tree, Pinus sylvestris Linnaeus (Pinaceae). We introduced mating pairs of woodwasps to stressed P. sylvestris at either high (15 mating pairs, nine trees) or low (two mating pairs, nine trees) density. More trees died, and more quickly, when exposed to the high versus low density of S. noctilio (78% versus 33% of trees). In the high-density treatment, year of tree death was synonymous with production of a S. noctilio F1 cohort (one-year or two-year generation time); this pattern was not as consistent in the low-density treatment. Although sample size was limited, our results indicate that attack density affects S. noctilio colonisation of P. sylvestris.
The Commensal Real-time Australian Square Kilometre Array Pathfinder Fast Transients survey is the first extensive astronomical survey using phased array feeds. Since January 2017, it has been searching for fast radio bursts in fly’s eye mode. Here, we present a calculation of the sensitivity and total exposure of the survey that detected the first 20 of these bursts, using the pulsars B1641-45 and B0833-45 as calibrators. The beamshape, antenna-dependent system noise, and the effects of radio-frequency interference and fluctuations during commissioning are quantified. Effective survey exposures and sensitivities are calculated as a function of the source counts distribution. Statistical ‘stat’ and systematics ‘sys’ effects are treated separately. The implied fast radio burst rate is significantly lower than the 37 sky−1 day−1 calculated using nominal exposures and sensitivities for this same sample by Shannon et al. (2018). At the Euclidean (best-fit) power-law index of −1.5 (−2.2), the rate is
(sys) ± 3.6 (stat) sky−1 day−1 (
(sys) ± 2.8 (stat) sky−1 day−1) above a threshold of 56.6 ± 6.6(sys) Jy ms (40.4 ± 1.2(sys) Jy ms). This strongly suggests that these calculations be performed for other FRB-hunting experiments, allowing meaningful comparisons to be made between them.
Mini-sabbaticals are formal short-term training and educational experiences away from an investigator’s home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.
In several recently published phylogenetic analyses, two Lower Devonian taxa, Doliodus and Pucapampella, both fall on the chondrichthyan stem, very close to the base of ‘conventionally defined chondrichthyans’ (i.e., forms possessing tessellated mineralization of the cartilaginous endoskeleton). These two taxa nevertheless exhibit strongly discordant morphologies from each other. A summary of the anatomical data concerning these taxa is presented here, including new, as well as previously published, findings. A new family Pucapampellidae is erected, containing Pucapampella and a newly recognized genus from South Africa. Morphological evidence is summarized for the monophyly of crown elasmobranchs (sharks and rays), holocephalans (chimaeras) and other chondrichthyans. Based on these data, Doliodus and pucapampellids both fall outside the chondrichthyan crown, but their relative phylogenetic positions on the chondrichthyan stem are unclear. Pucapampellid interrelationships are particularly hard to assess because little is known beyond their cranial and visceral arch morphology and also because pucapampellids possess a suite of ontogenetically primitive (and thus potentially neotenic) features. By contrast, the phylogenetic position of Doliodus seems less elusive; it possessed an ‘acanthodian-like’ complex of dermal spines, including pectoral fin spines, prepectoral, admedian, and prepelvic spines, and possibly dorsal and pelvic fin spines, in conjunction with numerous ‘chondrichthyan-like’ endoskeletal features and a heterodont ‘sharklike’ dentition. Doliodus can be viewed as a quintessential component of the evolutionary transition between ‘acanthodians’ and ‘conventionally defined chondrichthyans’, leaving little doubt that the chondrichthyan total group includes ‘acanthodians’ (now widely perceived to be a paraphyletic group, populating the basal part of the chondrichthyan stem). Although Doliodus has been resolved as a basal member of the ‘conventionally defined chondrichthyans’, it could occupy a more basal position on the chondrichthyan stem.