Designing Digital COVID-19 Screening: Insights and Deliberations

Due to the global COVID-19 pandemic, public health control and screening measures have been introduced at healthcare facilities, including those housing our most vulnerable populations. These warning measures situated at hospital entrances are presently labour-intensive, requiring additional staff to conduct manual temperature checks and risk-assessment questionnaires of every individual entering the premises. To make this process more efficient, we present eGate, a digital COVID-19 health-screening smart Internet of Things system deployed at multiple entry points around a children's hospital. This paper reports on design insights based on the experiences of concierge screening staff stationed alongside the eGate system. Our work contributes towards social-technical deliberations on how to improve design and deploy of digital health-screening systems in hospitals. It specifically outlines a series of design recommendations for future health screening interventions, key considerations relevant to digital screening control systems and their implementation, and the plausible effects on the staff who work alongside them

Dosage compensation can buffer copy- number variation in wild yeast

Abstract Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at 10-30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations-but they show elevated rates of gene amplification, suggesting that copynumber variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution

The molecular characterisation of Escherichia coli K1 isolated from neonatal nasogastric feeding tubes

Background: The most common cause of Gram-negative bacterial neonatal meningitis is E. coli K1. It has a mortality rate of 10–15%, and neurological sequelae in 30– 50% of cases. Infections can be attributable to nosocomial sources, however the pre-colonisation of enteral feeding tubes has not been considered as a specific risk factor. Methods: Thirty E. coli strains, which had been isolated in an earlier study, from the residual lumen liquid and biofilms of neonatal nasogastric feeding tubes were genotyped using pulsed-field gel electrophoresis, and 7-loci multilocus sequence typing. Potential pathogenicity and biofilm associated traits were determined using specific PCR probes, genome analysis, and in vitro tissue culture assays. Results: The E. coli strains clustered into five pulsotypes, which were genotyped as sequence types (ST) 95, 73, 127, 394 and 2076 (Achman scheme). The extra-intestinal pathogenic E. coli (ExPEC) phylogenetic group B2 ST95 serotype O1:K1:NM strains had been isolated over a 2 week period from 11 neonates who were on different feeding regimes. The E. coli K1 ST95 strains encoded for various virulence traits associated with neonatal meningitis and extracellular matrix formation. These strains attached and invaded intestinal, and both human and rat brain cell lines, and persisted for 48 h in U937 macrophages. E. coli STs 73, 394 and 2076 also persisted in macrophages and invaded Caco-2 and human brain cells, but only ST394 invaded rat brain cells. E. coli ST127 was notable as it did not invade any cell lines. Conclusions: Routes by which E. coli K1 can be disseminated within a neonatal intensive care unit are uncertain, however the colonisation of neonatal enteral feeding tubes may be one reservoir source which could constitute a serious health risk to neonates following ingestion

Very Low Mass Stellar and Substellar Companions to Solar-Like Stars From MARVELS V: A Low Eccentricity Brown Dwarf from the Driest Part of the Desert, MARVELS-6b

We describe the discovery of a likely brown dwarf (BD) companion with a minimum mass of 31.7 +/- 2.0 M_Jup to GSC 03546-01452 from the MARVELS radial velocity survey, which we designate as MARVELS-6b. For reasonable priors, our analysis gives a probability of 72% that MARVELS-6b has a mass below the hydrogen-burning limit of 0.072 M_Sun, and thus it is a high-confidence BD companion. It has a moderately long orbital period of 47.8929 +0.0063/-0.0062 days with a low eccentricty of 0.1442 +0.0078/-0.0073, and a semi-amplitude of 1644 +12/-13 m/s. Moderate resolution spectroscopy of the host star has determined the following parameters: T_eff = 5598 +/- 63, log g = 4.44 +/- 0.17, and [Fe/H] = +0.40 +/- 0.09. Based upon these measurements, GSC 03546-01452 has a probable mass and radius of M_star = 1.11 +/- 0.11 M_Sun and R_star = 1.06 +/- 0.23 R_Sun with an age consistent with less than ~6 Gyr at a distance of 219 +/- 21 pc from the Sun. Although MARVELS-6b is not observed to transit, we cannot definitively rule out a transiting configuration based on our observations. There is a visual companion detected with Lucky Imaging at 7.7 arcsec from the host star, but our analysis shows that it is not bound to this system. The minimum mass of MARVELS-6b exists at the minimum of the mass functions for both stars and planets, making this a rare object even compared to other BDs.Comment: 15 pages, 15 figures, 5 tables. Accepted for publication in The Astronomical Journa

HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease

DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration

Identification of functional genetic variation in exome sequence analysis

Recent technological advances have allowed us to study individual genomes at a base-pair resolution and have demonstrated that the average exome harbors more than 15,000 genetic variants. However, our ability to understand the biological significance of the identified variants and to connect these observed variants with phenotypes is limited. The first step in this process is to identify genetic variation that is likely to result in changes to protein structure and function, because detailed studies, either population based or functional, for each of the identified variants are not practicable. Therefore algorithms that yield valid predictions of a variant’s functional significance are needed. Over the past decade, several programs have been developed to predict the probability that an observed sequence variant will have a deleterious effect on protein function. These algorithms range from empirical programs that classify using known biochemical properties to statistical algorithms trained using a variety of data sources, including sequence conservation data, biochemical properties, and functional data. Using data from the pilot3 study of the 1000 Genomes Project available through Genetic Analysis Workshop 17, we compared the results of four programs (SIFT, PolyPhen, MAPP, and VarioWatch) used to predict the functional relevance of variants in 101 genes. Analysis was conducted without knowledge of the simulation model. Agreement between programs was modest ranging from 59.4% to 71.4% and only 3.5% of variants were classified as deleterious and 10.9% as tolerated across all four programs

HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease

DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer’s disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration

Very Low-Mass Stellar and Substellar Companions to Solar-Like Stars from MARVELS I: A Low Mass Ratio Stellar Companion to TYC 4110-01037-1 in a 79-day Orbit

TYC 4110-01037-1 has a low-mass stellar companion, whose small mass ratio and short orbital period are atypical amongst solar-like (Teff ~< 6000 K) binary systems. Our analysis of TYC 4110-01037-1 reveals it to be a moderately aged (~<5 Gyr) solar-like star having a mass of 1.07 +/- 0.08 MSun and radius of 0.99 +/- 0.18 RSun. We analyze 32 radial velocity measurements from the SDSS-III MARVELS survey as well as 6 supporting radial velocity measurements from the SARG spectrograph on the 3.6m TNG telescope obtained over a period of ~2 years. The best Keplerian orbital fit parameters were found to have a period of 78.994 +/- 0.012 days, an eccentricity of 0.1095 +/- 0.0023, and a semi-amplitude of 4199 +/- 11 m/s. We determine the minimum companion mass (if sin i = 1) to be 97.7 +/- 5.8 MJup. The system's companion to host star mass ratio, >0.087 +/- 0.003, places it at the lowest end of observed values for short period stellar companions to solar-like (Teff ~< 6000 K) stars. One possible way to create such a system would be if a triple-component stellar multiple broke up into a short period, low q binary during the cluster dispersal phase of its lifetime. A candidate tertiary body has been identified in the system via single-epoch, high contrast imagery. If this object is confirmed to be co-moving, we estimate it would be a dM4 star. We present these results in the context of our larger-scale effort to constrain the statistics of low mass stellar and brown dwarf companions to FGK-type stars via the MARVELS survey.Comment: 22 pages; accepted in A