Community-acquired pneumonia in children: cell-free plasma sequencing for diagnosis and management.

Community-acquired pneumonia (CAP) is a common cause of pediatric hospital admission. Empiric antibiotic therapy for hospitalized children with serious CAP now targets the most likely pathogen(s), including those that may demonstrate significant antibiotic resistance. Cell-free plasma next-generation sequencing (CFPNGS) was first made available for Pediatric Infectious Diseases physicians in June 1, 2017, to supplement standard-of-care diagnostic techniques. A retrospective chart review was performed for children hospitalized with CAP between June 1, 2017, and January 22, 2018, to evaluate the impact of CFPNGS. We identified 15 hospitalized children with CAP without other underlying medical conditions for whom CFPNGS was performed. CFPNGS identified a pathogen in 13 of 15 (86%) children compared with 47% for those using standard culture and PCR-based methods alone. Changes in antibiotic management were made in 7 of 15 (47%) of children as a result of CFPNGS

Using atmospheric trajectories to model the isotopic composition of rainfall in central Kenya

Publisher’s version made available under a Creative Commons license.The isotopic composition of rainfall (δ2H and δ18O) is an important tracer in studies of the ecohydrology, plant physiology, climate and biogeochemistry of past and present ecosystems. The overall continental and global patterns in precipitation isotopic composition are fairly well described by condensation temperature and Rayleigh fractionation during rainout. However, these processes do not fully explain the isotopic variability in the tropics, where intra-storm and meso-scale dynamics may dominate. Here we explore the use of atmospheric back-trajectory modeling and associated meteorological variables to explain the large variability observed in the isotopic composition of individual rain events at the study site in central Kenya. Individual rain event samples collected at the study site (n = 41) range from −51‰ to 31‰ for δ2H and the corresponding monthly values (rain volume-weighted) range from −15‰ to 15‰. Using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model, we map back-trajectories for all individual rain hours occurring at a research station in central Kenya from March 2010 through February 2012 (n = 544). A multiple linear regression analysis demonstrates that a large amount of variation in the isotopic composition of rainfall can be explained by two variables readily obtained from the HYSPLIT model: (1) solar radiation along the trajectory for 48 hours prior to the event, and (2) distance covered over land. We compare the measurements and regression model results to the isotopic composition expected from simple Rayleigh distillation along each trajectory. The empirical relationship described here has applications across temporal scales. For example, it could be used to help predict short-term changes in the isotopic composition of plant-available water in the absence of event-scale sampling. One can also reconstruct monthly, seasonal and annual weighted mean precipitation isotope signatures for a single location based only on hourly rainfall data and HYSPLIT model results. At the study site in East Africa, the annual weighted mean δ2H from measured and modeled values are −7.6‰ and −7.4‰, respectively, compared to −18‰ predicted for the study site by the Online Isotopes in Precipitation Calculator

Associations between polygenic risk for psychiatric disorders and substance involvement

Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European-American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium’s Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the 5 psychiatric disorders which comprised CROSS—attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)—and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p<0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: A) MDD PRS and non-problem cannabis use, B) MDD PRS and severe cocaine dependence, C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity

Incidence, remission and mortality of convulsive epilepsy in rural northeast South Africa

Background: Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. Methods: A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package. Results: The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)). Conclusions: The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa

The Geochemistry of Aubrites: Investigating Reduced Parent Bodies

The aubrites (~30 known meteorites) are a unique group of differentiated meteorites that formed on asteroids with oxygen fugacities (O2) from ~2 to ~6 log units below the iron-wstite buffer [12]. At these highly reduced conditions, elements deviate from the geochemical behavior exhibited at terrestrial O2, forming FeO-poor silicates, Si-bearing metals, and exotic sulfides [3]. Here we examine the 3D mineralogy and the geochemistry of fourteen aubrites, including mineral major element compositions, bulk-rock compositions, and oxygen isotopic compositions to understand their formation and evolution at extreme O2 conditions. While previous studies have described the petrology and 2D modal abundances of aubrites, this work investigates the 3D modal mineralogies of silicate, metal, and sulfide phases in aubrite samples, which are then com-pared to the available 2D data. We utilize X-ray computed tomography (XCT) to non-destructively analyze the distribution and abundances of mineral phases in aubrites and locate composite clasts of sulfide grains for future analysis

Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10−8/132 = 4 × 10−10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p \u3c 8.0 × 10−7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p \u3c 3.3 × 10−3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal

Symptom Clusters in Acute Myocardial Infarction: A Secondary Data Analysis

Background: Early recognition of acute myocardial infarction (AMI) symptoms and reduced time to treatment may reduce morbidity and mortality. People having AMI experience a constellation of symptoms, but the common constellations or clusters of symptoms have yet to be identified. Objectives: To identify clusters of symptoms that represent AMI. Methods: This was a secondary data analysis of nine descriptive, cross-sectional studies that included data from 1,073 people having AMI in the United States and England. Data were analyzed using latent class cluster analysis, an atheoretical method that uses only information contained in the data. Results: Five distinct clusters of symptoms were identified. Age, race, and sex were statistically significant in predicting cluster membership. None of the symptom clusters described in this analysis included all of the symptoms that are considered typical. In one cluster, subjects had only a moderate to low probability of experiencing any of the symptoms analyzed. Discussion: Symptoms of AMI occur in clusters, and these clusters vary among persons. None of the clusters identified in this study included all of the symptoms that are included typically as symptoms of AMI (chest discomfort, diaphoresis, shortness of breath, nausea, and lightheadedness). These AMI symptom clusters must be communicated clearly to the public in a way that will assist them in assessing their symptoms more efficiently and will guide their treatment-seeking behavior. Symptom clusters for AMI must also be communicated to the professional community in a way that will facilitate assessment and rapid intervention for AMI

Improving stamina and mobility with preop walking in surgical patients with frailty traits -OASIS IV: randomized clinical trial study protocol

BACKGROUND: Frail older surgical patients face more than a two-fold increase in postoperative complications, including myocardial infarction, deep vein thrombosis, pulmonary embolism, pneumonia, ileus, and others. Many of these complications occur because of postoperative loss of stamina and poor mobility. Preoperative exercise may better prepare these vulnerable patients for surgery. We present the protocol for our ongoing randomized trial to assess the impact of a preoperative walking intervention with remote coaching and pedometer on outcomes of stamina (six-minute walk distance- 6MWD) and mobility (postoperative steps) in older adults with frailty traits. METHODS: We will be conducting a randomized clinical trial with a total of 120 patients permitting up to a 33% rate of attrition, to reach a final sample size of 80 (with 40 patients for each study arm). We will include patients who are age 60 or higher, score 4 or greater on the Edmonton Frailty Scale assessment, and will be undergoing a surgical operation that requires a 2 or more night hospital stay to be eligible for our trial. Using block randomization stratified on baseline 6MWD, we will assign patients to wear a pedometer. At the end of three baseline days, an athletic trainer (AT) will provide a daily step count goal reflecting a 10-20% increase from baseline. Subsequently, the AT will call weekly to further titrate the goal or calls more frequently if the patient is not meeting the prescribed goal. Controls will receive general walking advice. Our main outcome is change in 6MWD on postoperative day (POD) 2/3 vs. baseline. We will also collect 6MWD approximately 4 weeks after surgery and daily in-hospital steps. CONCLUSION: If changes in a 6MWD and step counts are significantly higher for the intervention group, we believe this will confirm our hypothesis that the intervention leads to decreased loss of stamina and mobility. Once confirmed, we anticipate expanding to multiple centers to assess the interventional impact on clinical endpoints. TRIAL REGISTRATION: The randomized clinical trial was registered on clinicaltrials.gov under the identifier NCT03892187 on March 27, 2019