Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation.

Background: Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs). Methods: Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria. DEGs and DMPs between time points were detected using cell-type adjusted modeling with Cibersortx or IDOL, respectively. Results: Most major cell types and principal components had moderate to high correlation between the two deconvolution methods (r = 0.60-0.96). Estimates of cell-type proportions and DEGs or DMPs were largely unaffected by the method, with the greatest discrepancy in the estimation of neutrophils. Conclusion: Variation in cell-type proportions is captured similarly by both transcriptomic and methylome deconvolution methods for most major cell types.

Implementation of a Novel Tool to Collect Milk Feeding Data on Infants in Primary Care Clinics.

We aimed to capture milk feeding type in real time in a racially and socioeconomically diverse population. An electronic tool to assess milk feeding type at every medical visit for children aged 0 to 2 years was designed and incorporated into nursing workflows. The Milk Box tool was successfully added to the electronic clinical workspace of a large health system. There were eight clinics, with diverse characteristics, which incorporated the use of the Milk Box tool over 12 months. Time to 50% uptake of Milk Box varied from 3 to 5 months. Time to >80% uptake varied from 6 to 8 months. Our results show that Milk Box can be quickly incorporated into a clinical workflow when the team is given appropriate training and support. The tool also allows a primary care practice to study local breast milk consumption trends and to provide both individualized and system-level lactation support.

Influence of Early Lactation Assistance on Inpatient Exclusive Breastfeeding Rates.

BACKGROUND: Human milk feeding reduces the incidence and costs of several maternal and childhood illnesses. Initiation and success of human milk feeding are influenced by race, socioeconomic status, and family support. The influence of early in-hospital lactation assistance in breastfeeding success has been not well described. RESEARCH AIMS: We aimed to determine how suspected known factors influencing breastfeeding success influence in-hospital human milk feeding rates. Second, we aimed to examine how timing of lactation assistance is related to success of human milk feeding during the newborn hospitalization for healthy infants. METHODS: We conducted a retrospective cohort study of term infants born between January 1, 2014 and December 31, 2016 at a large tertiary academic hospital. We considered "success" to be 100% human milk feeding during the birth hospitalization, and compared differences in success by demographics, payor, race, and initial feeding preference. Influences of lactation assistance on success were analyzed using multivariable logistic regression. RESULTS: Mean success with exclusive human milk feeding among 7,370 infants was 48.9%, (n = 3,601). Successful participants were more likely to be 39-40 weeks' gestation (64.9%, n = 2,340), non-Hispanic/non-Latino (80.0%, n = 2,882), and using private insurance (69.2%, n = 2,491). Participants who had early feeding assisted by an International Board Certified Lactation Consultant (IBCLC) before being fed any formula were more likely to be successful than participants who had a feeding assisted by a non-IBCLC nurse (80% vs. 40% respectively). CONCLUSIONS: Success for exclusive human milk feeding during newborn hospitalization is strongly associated with several factors. Early intervention with IBCLCs can greatly improve breastfeeding success.

Improving Care for Critical Care Patients by Strategic Alignment of Quality Goals With a Physician Financial Incentive Model.

BACKGROUND AND OBJECTIVES: The passage of the Affordable Care Act has ignited a shift from the pay-for-performance model to value-based care with a particular relevance in critical care settings. Provider incentive programs are widely considered as a means to reward providers based on the achievement of preset quality metrics. This article aims to demonstrate the effects of a provider incentive program in the critical care delivery system in a large academic center in the Northeastern United States. METHODS: This article describes the results of a retrospective analysis of a performance-driven quality improvement initiative at a critical care facility of an academic medical center using a quasi-experimental pre-/posttest design. A set of quality measures was selected as outcome metrics. Selection criteria for the process measures are as follows: (i) the metric goals should be influenced by the physician's input to a large degree; (ii) the measure must be transparent and accessible within the hospital-wide data reporting system; (iii) the metric that required group effort and interdisciplinary collaboration to achieve; and (iv) the measure must directly affect patient outcome. The outcome metrics are central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs), standardized infection ratio (SIR), Foley catheter and central line utilization standardized utilization ratio (SUR), hand hygiene compliance, and adherence to respiratory recovery pathway goals. These metrics were tracked from for 3 years with success defined as achieving set benchmarks for each metric. RESULTS: The average CLABSI SIR and CAUTI SIR across all intensive care units (ICUs) decreased by 44% (P = .05) and 87% (P = .02) over 3 years as well as the central line and Foley catheter utilization falling by 41% and 30%, respectively. Hand hygiene compliance in the ICUs improved for the same period by 27 percentage points, as did compliance with the respiratory recovery pathway program by 4 percentage points. CONCLUSION: The use of a physician-driven financial incentive model in a critical care setting measured by outcome metrics dependent on physician input is successful with rigorous implementation and careful evaluation.

Toto, I've a Feeling We're Not in Kansas Anymore: Navigating the Mid-career Transition to Academic Medicine.

When physicians, nurse practitioners, and physician assistants transition from a community setting to a university-based academic environment during mid-career, it can be challenging. Strategic planning is needed to ensure success. Institutions can assist experienced providers making such a transition, and there are steps the provider can take to self-advocate. As a group of four medical professionals who began their careers in patient care community practices for up to 18 years before transitioning to an academic medical center, we have had to navigate an unfamiliar landscape. We collectively offer our tips for a successful mid-career transition to academic medicine.

Recent Trends in Infant Car Seat Tolerance Screening Failure Within a Large Health Care System, 2014-2018.

OBJECTIVES: To describe temporal trends in car seat tolerance screening (CSTS) failure within a large hospital system (2014-2018). METHODS: We conducted a retrospective cohort study using electronic medical record data for infants who underwent a CSTS. Our primary outcome measure was the CSTS failure rate. Covariates included year, CSTS location (well nursery or NICU), gestational age (GA), race, sex, birth weight, CSTS date, and age at CSTS. Associations of covariates with CSTS failure were examined by using χ2 tests, t tests, analysis of variance, and Wilcoxon rank tests. Multivariable logistic regression was used to determine the adjusted odds of CSTS failure. RESULTS: Of 4849 infants tested, the failure rate was 8.1% (n = 394). Most CSTS occurred in the well nursery (79.5%) and involved late preterm (55.2%) or term infants (23.7%). In bivariate analyses, year, unit location, higher birth weight, younger chronological age at testing, and higher GA were positively associated with CSTS failure (P < .05). After stratification by CSTS location, the CSTS failure rate rose in the well nursery but remained stable in the NICU, and use of screening rose among term infants. In the adjusted model, year, GA, and corrected gestational age at CSTS were associated with failure. Each subsequent year was associated with a 19% increase in odds of CSTS failure (P < .001). CONCLUSIONS: We found a higher rate of CSTS failure in the well nursery compared with the NICU, and the difference in failure rates increased over time. Improved understanding of infants at the highest risk of CSTS failure could impact routine screening guidelines.

Bloodmeal Host Selection of Culex quinquefasciatus (Diptera: Culicidae) in Las Vegas, Nevada, United States.

St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) have recently emerged in the southwestern United States. Surveillance for arboviruses in Las Vegas, NV, detected a surge of SLEV activity in the southern house mosquito (Culex quinquefasciatus Say) during 2016. To identify candidate avian amplifiers, we assessed the identification, viral infection, and immune status of vertebrate hosts for 195 blood-engorged Cx. quinquefasciatus mosquitoes collected in August and September 2016. Bloodmeals were identified from 164 engorged abdomens, representing 19 species of birds and three species of mammals. No SLEV or WNV viremia was detected, but one mosquito tested positive for Culex flavivirus. House finch (Haemorhous mexicanus) (Muller) was the most common bloodmeal, followed by domestic chicken (Gallus gallus) (Linnaeus), American robin (Turdus migratorius) L., house sparrow (Passer domesticus) (L.), great-tailed grackle (Quiscalus mexicanus) (Gmelin), northern mockingbird (Mimus polyglottos) (L.) and mourning dove (Zenaida macroura) (L.). SLEV-reactive antibodies were detected in six identified bloodmeals and WNV-reactive antibodies were detected in 33. House sparrow and house finch were the most likely hosts to show previous exposure to SLEV and WNV, respectively. Over-utilization by Cx. quinquefasciatus for bloodmeal hosts was observed primarily among robin, finch and sparrow, all species that roost communally. House finch stands out as a candidate important amplifier for both SLEV and WNV because of its preference by mosquito vectors, and high competence for closely related virus strains. While implicated in previous outbreaks as an important mosquito vector, Cx. quinquefasciatus feeds infrequently on mammals in Las Vegas, indicating a low risk for bridge transmission to humans.

Zika Virus Surveillance at the Human-Animal Interface in West-Central Brazil, 2017-2018.

Zika virus (ZIKV) was first discovered in 1947 in Uganda but was not considered a public health threat until 2007 when it found to be the source of epidemic activity in Asia. Epidemic activity spread to Brazil in 2014 and continued to spread throughout the tropical and subtropical regions of the Americas. Despite ZIKV being zoonotic in origin, information about transmission, or even exposure of non-human vertebrates and mosquitoes to ZIKV in the Americas, is lacking. Accordingly, from February 2017 to March 2018, we sought evidence of sylvatic ZIKV transmission by sampling whole blood from approximately 2000 domestic and wild vertebrates of over 100 species in West-Central Brazil within the active human ZIKV transmission area. In addition, we collected over 24,300 mosquitoes of at least 17 genera and 62 species. We screened whole blood samples and mosquito pools for ZIKV RNA using pan-flavivirus primers in a real-time reverse-transcription polymerase chain reaction (RT-PCR) in a SYBR Green platform. Positives were confirmed using ZIKV-specific envelope gene real-time RT-PCR and nucleotide sequencing. Of the 2068 vertebrates tested, none were ZIKV positive. Of the 23,315 non-engorged mosquitoes consolidated into 1503 pools tested, 22 (1.5%) with full data available showed some degree of homology to insect-specific flaviviruses. To identify previous exposure to ZIKV, 1498 plasma samples representing 62 species of domestic and sylvatic vertebrates were tested for ZIKV-neutralizing antibodies by plaque reduction neutralization test (PRNT90). From these, 23 (1.5%) of seven species were seropositive for ZIKV and negative for dengue virus serotype 2, yellow fever virus, and West Nile virus, suggesting potential monotypic reaction for ZIKV. Results presented here suggest no active transmission of ZIKV in non-human vertebrate populations or in alternative vector candidates, but suggest that vertebrates around human populations have indeed been exposed to ZIKV in West-Central Brazil.

Circadian rhythms of trematode parasites: applying mixed models to test underlying patterns.

Circadian rhythms of parasites and their hosts can influence processes such as transmission, pathology and life cycle evolution. For trematode parasites that depend on free-living infectious stages (i.e. cercariae) to move among host species, the timing of parasite release is hypothesized to increase the likelihood of contacting a host. Yet, a persistent challenge in studying such biorhythms involves selection of appropriate analytical techniques. Here, we extend a generalized linear mixed modelling (GLMM) framework to cosinor analyses, thereby allowing flexibility in the statistical distribution of the response variable, incorporation of multiple covariates and inclusion of hierarchical grouping effects. By applying this approach to 93 snails infected with trematode parasites from freshwater pond ecosystems, we detected non-random rhythms in six of eight species, with variation in both the timing of peak cercariae release (between 5:10 and 21:46 h) and its magnitude (between 13 and 386). The use of GLMM yielded more accurate and precise estimates of the cosinor parameters compared with classical least-squares (LS) based on a simulation-based sensitivity analysis. The sensitivity analysis revealed that the amplitude and rhythm-adjusted mean values from the LS models diverged from the true values at some limits. We highlight the importance of novel analytical approaches for evaluating parasite circadian rhythms and investigating their underlying mechanisms.

Applying fMRI complexity analyses to the single subject: a case study for proposed neurodiagnostics.

Nonlinear dynamic tools have been statistically validated at the group level to identify subtle differences in system wide regulation of brain meso-circuits, often increasing clinical sensitivity over conventional analyses alone. We explored the feasibility of extracting information at the single-subject level, illustrating two pairs of healthy individuals with psychological differences in stress reactivity. We applied statistical and nonlinear dynamic tools to capture key characteristics of the prefrontal-limbic loop. We compared single subject results with statistical results for the larger group. We concluded that complexity analyses may identify important differences at the single-subject level, supporting their potential towards neurodiagnostic applications.

Getting to zero: Reduction in the incidence of multidrug-resistant organism infections using an integrated infection control protocol in an intensive care unit.

Environmental cleaning is a vital component of infection control. We describe the use of an integrated infection control protocol in an intensive care unit and its influence on multidrug-resistant organism infection rates. Sustained reductions in multidrug-resistant organism infections can be achieved if individual processes and weaknesses in intensive care unit environments are identified and addressed in a systematic and comprehensive manner.

Endohelminths in Bird Hosts from Northern California and an Analysis of the Role of Life History Traits on Parasite Richness.

The life history characteristics of hosts often influence patterns of parasite infection either by affecting the likelihood of parasite exposure or the probability of infection after exposure. In birds, migratory behavior has been suggested to affect both the composition and abundance of parasites within a host, although whether migratory birds have more or fewer parasites is unclear. To help address these knowledge gaps, we collaborated with airports, animal rescue/rehabilitation centers, and hunter check stations in the San Francisco Bay Area of California to collect 57 raptors, egrets, herons, ducks, and other waterfowl for parasitological analysis. After dissections of the gastrointestinal tract of each host, we identified 64 taxa of parasites: 5 acanthocephalans, 24 nematodes, 8 cestodes, and 27 trematodes. We then used a generalized linear mixed model to determine how life history traits influenced parasite richness among bird hosts, while controlling for host phylogeny. Parasite richness was greater in birds that were migratory with larger clutch sizes and lower in birds that were herbivorous. The effects of clutch size and diet are consistent with previous studies and have been linked to immune function and parasite exposure, respectively, whereas the effect of migration supports the hypothesis of "migratory exposure" rather than that of "migratory escape."

Distracted by distractors: eye movements in a dynamic inattentional blindness task.

Inattentional Blindness (IB) occurs when observers engaged in resource-consuming tasks fail to see unexpected stimuli that appear in their visual field. Eye movements were recorded in a dynamic IB task where participants tracked targets amongst distractors. During the task, an unexpected stimulus crossed the screen for several seconds. Individuals who failed to report the unexpected stimulus were deemed to be IB. Being IB was associated with making more fixations and longer gaze times on distractor stimuli, being less likely to fixate the unexpected stimulus, and having lower working memory capacity than those who were not IB. Noticing the unexpected stimulus was not contingent upon fixating it, suggesting that some individuals processed the unexpected stimulus via covert attention. The findings support earlier research on working memory and IB. In addition, IBs were less efficient attentional allocators than those who were not IB, as reflected in their eye tracking of irrelevant distractors.

Is inattentional blindness related to individual differences in visual working memory capacity or executive control functioning?

Inattentional blindness (IB) research deals with situations where, under focused attention tasks, salient stimuli that are irrelevant to that task do not reach conscious awareness. Although such research has captured popular imagination, to date very little research has been conducted on whether some are more likely to experience this phenomenon than others. Here we provide evidence that working memory capacity (WMC) contributed to this experience, with lower WMC being predictive of IB. We also investigated whether IB could be more readily explained in terms of domain-specific visual WMC. No group differences in visual WMC were found, nor any differences in the ability to perform the primary IB task. These findings suggest that differences in higher-order executive control of attention contributes to the experience of IB.

Predicting and manipulating the incidence of inattentional blindness.

Inattentional blindness (IB) occurs when an observer, who is engaged in a resource-consuming task, fails to notice an unexpected although salient stimulus appearing in their visual field. The incidence of IB is affected by changes in stimulus-driven properties, but little research has examined individual differences in IB propensity. We examine working memory capacity (WMC), processing styles (flicker task), inhibition (Stroop task), and training in predicting IB. WMC is associated with IB (Experiments 1 and 2) but neither processing style (Experiment 1) nor inhibition (Experiment 2) was associated. In Experiment 2, prior training on a task reduced the incidence of IB compared to no prior training, and this effect was significantly larger when trained on the same tracking task as that used in the IB task rather than a different task. We conclude that IB is related to WMC and that training can influence the incidence of IB.

Intravenous iloprost increases mesenteric blood flow in experimental acute nonocclusive mesenteric ischemia.

OBJECTIVE: To evaluate the effect of an intravenously administered synthetic epoprostenol analog, iloprost, in nonocclusive acute mesenteric ischemia induced by cardiac tamponade. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Animal research laboratory at a university medical center. SUBJECTS: Ten Yorkshire pigs (weight range, 20-25 kg). INTERVENTIONS: Nonocclusive acute mesenteric ischemia was induced by pericardial tamponade. Pigs were randomized to receive either a low-dose, continuous intravenous infusion of iloprost (0.075 microg/kg/min) or an equivalent volume of normal saline to serve as the control. Infusion of iloprost or saline was continued after pericardial tamponade was reversed. METHODS: Ten anesthetized and ventilated pigs underwent laparotomy and thoracotomy. A pulmonary artery catheter was inserted, a magnetic flow probe was positioned around the superior mesenteric artery (SMA), and cannulation of the pericardial space was performed. Pericardial tamponade was induced by injecting 5% dextrose in water into the pericardial space until blood flow in the superior mesenteric artery decreased to half of baseline. After 60 mins, animals received either a continuous intravenous infusion of iloprost at 0.075 microg/kg/min (n = 6) or an equal volume of normal saline (n = 4) for 60 mins. Pericardial fluid was then removed, and iloprost or normal saline infusion was continued for another 60 mins. MEASUREMENTS: Heart rate, blood pressure, cardiac output, oxygen delivery, oxygen consumption, SMA blood flow, ileal Pco2, ileal intramucosal pH, and serum lactate levels of mixed venous blood and mesenteric venous blood were recorded at baseline, after pericardial tamponade was induced, during the iloprost or normal saline infusion with pericardial tamponade, and after removal of pericardial fluid (reperfusion period). RESULTS: Iloprost infusion increased SMA blood flow by 60% in this model of nonocclusive mesenteric ischemia (from 168 +/- 41 to 269 +/- 76 mL/min; p <.05). The effect of iloprost infusion was more prominent after the tamponade (422 +/- 87 mL/min in the iloprost group vs. 232 +/- 111 mL/min in the control group; p <.05). Increased mesenteric perfusion decreased intestinal mucosal hypercarbia, leading to improvement of intramucosal pH.