Coccolithoviruses (Phycodnaviridae) infect and lyse the most ubiquitous and successful coccolithophorid in modern oceans, Emiliania huxleyi. So far, the genomes of 13 of these giant lytic viruses ...(i.e., Emiliania huxleyi viruses-EhVs) have been sequenced, assembled, and annotated. Here, we performed an in-depth comparison of their genomes to try and contextualize the ecological and evolutionary traits of these viruses. The genomes of these EhVs have from 444 to 548 coding sequences (CDSs). Presence/absence analysis of CDSs identified putative genes with particular ecological significance, namely sialidase, phosphate permease, and sphingolipid biosynthesis. The viruses clustered into distinct clades, based on their DNA polymerase gene as well as full genome comparisons. We discuss the use of such clustering and suggest that a gene-by-gene investigation approach may be more useful when the goal is to reveal differences related to functionally important genes. A multi domain "Best BLAST hit" analysis revealed that 84% of the EhV genes have closer similarities to the domain Eukarya. However, 16% of the EhV CDSs were very similar to bacterial genes, contributing to the idea that a significant portion of the gene flow in the planktonic world inter-crosses the domains of life.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PURPOSE: We sought to determine the effects of a communication process that was designed to encourage the use of advanced supportive technology when it is of benefit, but to limit its burdens when it ...is ineffective. We compared usual care with a proactive, multidisciplinary method of communicating that prospectively identified for patients and families the criteria that would determine whether a care plan was effective at meeting the goals of the patient. This process allowed caregivers to be informed of patient preferences about continued advanced supportive technology when its continuation would result in a compromised functional outcome or death.
MATERIALS AND METHODS: We performed a before-and-after study in 530 adult medical patients who were consecutively admitted to a university tertiary care hospital for intensive care. Multidisciplinary meetings were held within 72 hours of critical care admission. Patients, families, and the critical care team discussed the care plan and the patients’ goals and expectations for the outcome of critical care. Clinical “milestones” indicative of recovery were identified with time frames for their occurrence. Follow-up meetings were held to discuss palliative care options when continued advanced supportive technology was not achieving the patient’s goals. We measured length of stay, mortality, and provider team and family consensus in 134 patients before the intensive communication intervention and in 396 patients after the intervention.
RESULTS: Intensive communication significantly reduced the median length of stay from 4 days (interquartile range, 2 to 11 days) to 3 days (2 to 6 days,
P = 0.01 by survival analysis). This reduction remained significant after adjustment for acute physiology and chronic health evaluation (APACHE) 3 score risk ratio (RR) = 0.81; 95% confidence interval (CI), 0.66 to 0.99;
P = 0.04). Subgroup analysis revealed that this reduction occurred in our target group, patients with acuity scores in the highest quartile who died (RR = 0.60; 95% CI, 0.38 to 0.92;
P = 0.02). The intervention, which allowed dying patients earlier access to palliative care, was not associated with increased mortality.
CONCLUSIONS: Intensive communication was associated with a reduction in critical care use by patients who died. Our multidisciplinary process targeted advanced supportive technology to patients who survived and allowed the earlier withdrawal of advanced supportive technology when it was ineffective.
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GEOZS, IJS, NUK, OILJ, UL, UM
The sloths that dispersed into Central and North America were most likely derived from tropical taxa, as indicated by their high occlusal surface area (OSA) in comparison with body mass, as in South ...American tropical species. Relative muzzle width and hypsodonty indices were used to infer the dietary adaptation of several Late Pleistocene/Early Holocene giant ground sloths from the Americas. Nothrotheriidae and Megatheridae taxa were adapted to a browser or browsing mixedfeeder diet, Mylodontidae taxa to a variety of dietary types, and Megalonychidae taxa to a browsing mixedfeeder diet. However, these are generalized dietary adaptations and do not necessarily reflect the consumption of specific food resources. In general, Megalonychidae and Nothrotheriidae were climbing species, Mylodontidae were digging species, and Megatheriidae were fully terrestrial species.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Medication dosing errors are common in prehospital pediatric patients. Prior work has shown the overall medication error rate by emergency medical services (EMS) in Michigan was 34.7%. To reduce ...these errors, the state of Michigan implemented a pediatric dosing reference in 2014 listing medication doses and volume to be administered.
To examine changes in pediatric dosing errors by EMS in Michigan after implementation of the pediatric dosing reference.
We conducted a retrospective review of the Michigan Emergency Medical Services Information System of children ≤ 12 years of age from June 2016-May 2017 treated by 16 EMS agencies. Agencies were a mix of public, private, third-service, and fire-based. A dosing error was defined as >20% deviation from the weight-appropriate dose listed on the pediatric dosing reference. Descriptive statistics with confidence intervals and standard deviations are reported.
During the study period, there were 9,247 pediatric encounters, of whom 727 (7.9%) received medications and are included in the study. There were 1078 medication administrations, with 380 dosing errors (35.2% 95% CI 25.3-48.4). The highest error rates were for dextrose 50% (3/4 or 75% 95% CI 32.57-100.0) and glucagon (3/4 or 75% 95% CI 32.57-100.0). The next highest proportions of incorrect doses were opioids: intranasal fentanyl (11/16 or 68.8% 95% CI 46.04-91.46) and intravenous fentanyl (89/130 or 68.5% 95% CI 60.47-76.45). Morphine had a much lower error rate (24/51 or 47.1% 95% CI 33.36-60.76). Midazolam had the third highest error rate, for intravenous (27/50 or 54.0% 95% CI (40.19-67.81) and intramuscular (25/68 or 36.8% 95% CI 40.19-67.81) routes. Epinephrine 1 mg/10 ml had an incorrect dosage rate of 35/119 (29.4% 95% CI 20.64-36.99). Asthma medications had the lowest rate of incorrect dosing (albuterol sulfate 9/247 or 3.6% 95% CI 1.31-5.98).
Medications administered to prehospital pediatric patients continue to demonstrate dosing errors despite pediatric dosing reference implementation. Although there have been improvements in error rates in asthma medications, the overall error rate has increased. Continued work to build patient safety strategies to reduce pediatric medication dosing errors by EMS is needed.
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IJS, NUK, OILJ, UL, UM, UPUK
Ducks are the reservoir hosts of avian influenza viruses (AIV) and do not display signs of disease when infected. AIV are frequently transmitted to chickens from free‐flying ducks where they may ...cause significant disease and pose a threat to the poultry industry because they can disrupt trade and reduce production. This difference in clinical disease may be due to the host's response to infection. In this report we focus on the expression of key cytokines and proteins: IL‐1 β, IL‐2, and the type I interferons and their expression in response to a duck‐origin AIV, in both host systems. Peripheral blood mononuclear cells (PBMC) from chickens and ducks, were cultured, and infected with AIV. The fold‐change in expression levels of antiviral cytokines was determined using RRTPCR. While both species responded to infection with a robust interferon response, IL‐1 β and IL‐2 cytokine responses differed dramatically. In ducks, IL‐1 β was strongly suppressed, while IL‐2 was induced nearly 30‐fold, implying the activation of a CTL response. In contrast, IL‐1 β was induced nearly 20‐fold in chicken PBMC over the course of the experiment, suggesting a strong pro‐inflammatory response, while IL‐2 expression remained at baseline levels. AIV infection of chicken PBMC induced significant cell death, whereas duck PBMC were viable at 36 hours pi. These cytokine responses indicate different strategies used by 2 species in response to AIV.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Identifying stars belonging to different classes is vital in order to build up statistical samples of different phases and pathways of stellar evolution. In the era of surveys covering ...billions of stars, an automated method of identifying these classes becomes necessary. Methods Many classes of stars are identified based on their emitted spectra. In this paper, we use a combination of multi-class multi-label methods from Machine Learning (ML) and the PySSED spectral-energy-distribution fitting algorithm to classify stars into nine different classes. The classifier is trained on subsets of the SIMBAD database. Particular challenges are the very high sparsity (large fraction of missing values) of the underlying data as well as the high class imbalance. We discuss the different variables available, such as photometric measurements on the one hand, and indirect predictors such as Galactic position on the other hand. Results We show the difference in performance when excluding certain variables, and discuss in which contexts which variables should be used. Finally, we show that increasing the number of samples of a particular type of star significantly increases the performance of the model for that particular type, while having little to no impact on other types. Conclusions While the current accuracy of the classifier is not high enough to be usable for non-experts, this work is an initial proof of feasibility for using ML to classify stars.
The Influenza A Virus (IAV) employs a variety of strategies in order to disarm the host immune response, most of which are carried out by the non-structural 1 protein encoded in the eighth viral ...genome segment. One such strategy is to blunt the innate immune response by preventing the expression of the type I interferons (IFN), other pro-inflammatory cytokines and immune-related genes. Disruption of the interferon-signaling pathway is a central component of viral infection in both mammalian and avian hosts. However, there is considerable variability in virus capacity to disrupt this signaling pathway as well as variation between species of the host expression of immune-related genes in response to infection with the same virus. Moreover, the clinical outcomes of viral infection differ among avian species; ducks harbor persistent, asymptomatic infections, where chickens display more robust responses and present symptomatically with respiratory signs, decreased egg production, and mortality. Avian species are not well understood as hosts of IAV. The general roles of avian species in the transmission, perpetuation, and evolution of IAV is well known although detailed information is lacking including knowledge of avian immune responses and their regulation by IAV. As a consequence, IAV from birds are frequently adapted to and subsequently assessed in mammalian hosts such as mice and ferrets for immune function and viral transmission studies, the results of which are extrapolated to encompass the generic non-human response to avian influenza. To address this gap in knowledge regarding the avian response to IAV, the following chapters of this thesis describe the early responses to IAV infection on a molecular signaling level and compare them in cells derived from chickens and ducks. In Chapter 2, by infecting peripheral blood mononuclear cells (PBMC) from avian hosts that have differences in responses to IAV infection and play different roles in the natural history of IAV with the same low pathogenic avian influenza virus, we identified differences in the expressions of key immune-related genes. Interestingly, the cytopathic effect of the virus was evident in chicken cells, whereas duck cells displayed no evidence of infection. Furthermore, the in vitro cytokine and immune-gene expression profiles between the two host's differed. Specifically pro-inflammatory molecules IL-1β and IL-6 were highly upregulated in chicken cells, whereas duck cells expressed baseline levels, and a similar pattern was observed for both IFN-β and IFN-γ. Taken together, these patterns suggest a molecular mechanism for observed clinical presentation. Low pro-inflammatory and IFN levels are consistent with an asymptomatic response to IAV infections in ducks, while the robust responses in chickens are more consistent with symptomatic infections. These findings provide valuable insight into the IFN expression patterns induced by IAV and differences between the responses of avian hosts. A canonical response to avian IAV infections has been reported in mammalian hosts, where the IAV NS1 protein, antagonizes the expression of type I IFN at multiple levels of the cellular pathway. It is less clear how NS1 interacts with avian cellular proteins, and whether viral suppression of IFN expression is similar in birds generally or if the mechanism and magnitude of expression differs between the major classes of avian hosts. To further complicate the issue, the NS1 gene exists as two allelic variants. One variant, the A allele, has been identified in viruses infecting all susceptible hosts, mammalian and avian. The other variant, the B allele, is almost exclusively isolated from viruses infecting avian hosts with few exceptions. The two alleles are only 69% identical at the amino acid level, and the sequence differences imply the two alleles may function differently. The second aim in this body of work was to characterize the in vitro innate immune gene (the type I IFNs and downstream cytokines) expression of chickens, turkeys, and ducks in response to infection with A allele or the B allele reassortant viruses. This study identified key differences and similarities between the two alleles. First, viruses bearing the A allele replicated to higher titers in the cells of chickens and turkeys (species which share a more recent ancestor), whereas viruses bearing the B allele replicated to higher titer in duck cells (species more distantly related to chickens and turkeys). Second, the B allele also suppressed the expression of IFN-β more effectively than did the A allele at a single time point in chicken and turkey cells. The differences between the alleles ended there; both A and B allele NS1 proteins modulated the expression of the other type I IFN and their downstream effector proteins Mx and 2'-5' oligoadenylate synthetase to similar extents. Chimeric constructs of the NS1 gene were used to identify regions of the NS1 gene responsible for the differences in replication titers and the expression of IFN-β in chicken cells between A and B alleles. This assay identified the nucleotides spanning positions 1-164 as responsible for the differences in viral replication, whereas nucleotide positions 164-541 were responsible for the differences in IFN-β expression in chicken cells. Combined, these results form the first comprehensive study of IAV and NS1 alleles in avian species. The final aim of this study was to characterize the geographic distribution, prevalence, and selective pressure driving amino acid changes of the NS1 alleles in viruses isolated from North American chickens, turkeys, and ducks. In addition to online databases, sequences were obtained from the California H6N2 outbreak in chickens, which took place between 2000 and 2005. This study identified a higher than expected proportion of B alleles in circulation from 2002-2012. Interestingly, the H6N2 viruses were associated with a mixed population of viruses bearing either the A or the B allele, which is unusual since other outbreaks were associated with only one NS1 sequence. Lastly, a novel approach to identifying selective pressures was employed by examining the ratio of nonsynonymous to synonymous substitutions of specific functional regions of the NS1 gene and compared to the ratio of the entire gene. This approach identified that the carboxyl terminus of the NS1 gene is undergoing positive selective pressure which is driving variation in this region.
IntroductionThe PROUD (Prevalence of Metabolic diseases and their Influence on Macrovascular Disease and Fractures in Barranquilla) study was initiated to assess the prevalence and identify unique ...risk factors for major diseases and mortality in a community health program.MethodsFrom 2003 to 2016, PROUD enrolled 11,941 participants and collected their baseline medical history, demographics, anthropometric and clinical measurements. The participants were followed for a median of 10 years (range 1-14). Overall mortality with specific causes was obtained or censored for survivors in August 2017. We applied random survival forest (RSF), a machine learning approach, to identify predictors of mortality, stratified by gender. Top predictors were selected to construct multivariate Cox regression models for risk prediction.ResultsAt baseline, participants’ median age was 64 years (range 18-96), with 83% women, 15% diabetes, 38% hypertension, 35% hypercholesterolemia, 19% hypertriglyceridemia, and 17% bone fractures. During follow-up, 1,126 deaths occurred, with a 10-year mortality of 10.5%, that differed by gender (men12.3% vs. women10%, P=0.001). Of over 70 baseline factors, RSF identified age, diabetes, marital status, hypertension, systolic blood pressure, body mass index, weight, waist/hip ratio, heart attack, stroke, heart rate, fruits and alcohol consumption were univariately associated with mortality for both genders (all P<0.01). Additionally, fractures, cancer, exercise, age at menarche and number of pregnancies were related to mortality in women (all P<0.01). Multivariate Cox regression analyses were congruent with RSF findings (Table 1).ConclusionIn this first large population health study of Barranquilla, gender-specific differences in predictors of mortality were identified. This on-going PROUD data analysis will provide new tools for disease outcome assessment and help develop prevention and treatment programs for the community.
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