Strain level and comprehensive microbiome analysis in inflammatory bowel disease via multi-technology meta-analysis identifies key bacterial influencers of disease

Inflammatory bowel disease (IBD) is a heterogenous disease in which the microbiome has been shown to play an important role. However, the precise homeostatic or pathological functions played by bacteria remain unclear. Most published studies report taxa-disease associations based on single-technology analysis of a single cohort, potentially biasing results to one clinical protocol, cohort, and molecular analysis technology. To begin to address this key question, precise identification of the bacteria implicated in IBD across cohorts is necessary. We sought to take advantage of the numerous and diverse studies characterizing the microbiome in IBD to develop a multi-technology meta-analysis (MTMA) as a platform for aggregation of independently generated datasets, irrespective of DNA-profiling technique, in order to uncover the consistent microbial modulators of disease. We report the largest strain-level survey of IBD, integrating microbiome profiles from 3,407 samples from 21 datasets spanning 15 cohorts, three of which are presented for the first time in the current study, characterized using three DNA-profiling technologies, mapping all nucleotide data against known, culturable strain reference data. We identify several novel IBD associations with culturable strains that have so far remained elusive, including two genome-sequenced but uncharacterized Lachnospiraceae strains consistently decreased in both the gut luminal and mucosal contents of patients with IBD, and demonstrate that these strains are correlated with inflammation-related pathways that are known mechanisms targeted for treatment. Furthermore, comparative MTMA at the species versus strain level reveals that not all significant strain associations resulted in a corresponding species-level significance and conversely significant species associations are not always re-captured at the strain level. We propose MTMA for uncovering experimentally testable strain-disease associations that, as demonstrated here, are beneficial in discovering mechanisms underpinning microbiome impact on disease or novel targets for therapeutic interventions

Feasibility and safety of planned early discharge following laparotomy in gynecologic oncology with enhanced recovery protocol including opioid-sparing anesthesia

ObjectiveThis study aims to evaluate the feasibility and safety of planned postoperative day 1 discharge (PPOD1) among patients who undergo laparotomy (XL) in the department of gynecology oncology utilizing a modified enhanced recovery after surgery (ERAS) protocol including opioid-sparing anesthesia (OSA) and defined discharge criteria.MethodsPatients undergoing XL and minimally invasive surgery (MIS) were enrolled in this prospective, observational cohort study after the departmental implementation of a modified ERAS protocol. The primary outcome was quality of life (QoL) using SF36, PROMIS GI, and ICIQ-FLUTS at baseline and 2- and 6-week postoperative visits. Statistical significance was assessed using the two-tailed Student's t-test and non-parametric Mann–Whitney two-sample test.ResultsOf the 141 subjects, no significant demographic differences were observed between the XL group and the MIS group. The majority of subjects, 84.7% (61), in the XL group had gynecologic malignancy [vs. MIS group; 21 (29.2%), p < 0.001]. All patients tolerated OSA. The XL group required higher intraoperative opioids [7.1 ± 9.2 morphine milligram equivalents (MME) vs. 3.9 ± 6.9 MME, p = 0.02] and longer surgical time (114.2 ± 41 min vs. 96.8 ± 32.1 min, p = 0.006). No significant difference was noted in the opioid requirements at the immediate postoperative phase and the rest of the postoperative day (POD) 0 or POD 1. In the XL group, 69 patients (73.6%) were successfully discharged home on POD1. There was no increase in the PROMIS score at 2 and 6 weeks compared to the preoperative phase. The readmission rates within 30 days after surgery (XL 4.2% vs. MIS 1.4%, p = 0.62), rates of surgical site infection (XL 0% vs. MIS 2.8%, p = 0.24), and mean number of post-discharge phone calls (0 vs. 0, p = 0.41) were comparable between the two groups. Although QoL scores were significantly lower than baseline in four of the nine QoL domains at 2 weeks post-laparotomy, all except physical health recovered by the 6-week time point.ConclusionsPPOD1 is a safe and feasible strategy for XL performed in the gynecologic oncology department. PPOD1 did not increase opioid requirements, readmission rates compared to MIS, and patient-reported constipation and nausea/vomiting compared to the preoperative phase

Diversity and abundance of pteropods and heteropods along a latitudinal gradient across the Atlantic Ocean

AbstractShelled pteropods and heteropods are two independent groups of holoplanktonic gastropods that are potentially good indicators of the effects of ocean acidification. Although insight into their ecology and biogeography is important for predicting species-specific sensitivities to ocean change, the species abundances and biogeographical distributions of pteropods and heteropods are still poorly known. Here, we examined abundance and distribution patterns of pteropods (euthecosomes, pseudothecosomes, gymnosomes) and heteropods at 31 stations along a transect from 46°N to 46°S across the open waters of the Atlantic Ocean (Atlantic Meridional Transect cruise AMT24). We collected a total of 7312 pteropod specimens belonging to at least 31 species. Pteropod abundances were low north of 40°N with <15 individuals per 1000m3, varied between 100 and 2000ind./1000m3 between 30°N and 40°S, and reached >4000ind./1000m3 just south of 40°S. This accounted for an estimated biomass of 3.2mgm−3 south of 40°S and an average of 0.49mgm−3 along the entire transect. Species richness of pteropods was highest in the stratified (sub)tropical waters between 30°N and 30°S, with a maximum of 15 species per station. The biogeographical distribution of pteropod assemblages inferred by cluster analysis was largely congruent with the distribution of Longhurst’s biogeochemical provinces. Some pteropod species distributions were limited to particular oceanographic provinces, for example, subtropical gyres (e.g. Styliola subula) or warm equatorial waters (e.g. Creseis virgula). Other species showed much broader distributions between ∼35°N and ∼35°S (e.g. Limacina bulimoides and Heliconoides inflatus). We collected 1812 heteropod specimens belonging to 18 species. Highest heteropod abundances and species richness were found between 30°N and 20°S, with up to ∼700ind./1000m3 and a maximum of 14 species per station. Heteropods were not restricted to tropical and subtropical waters, however, as some taxa were also relatively abundant in subantarctic waters. Given the variation in distribution patterns among pteropod and heteropod species, it is likely that species will differ in their response to ocean changes

Ceruloplasmin Deficiency Reduces Levels of Iron and BDNF in the Cortex and Striatum of Young Mice and Increases Their Vulnerability to Stroke

Ceruloplasmin (Cp) is an essential ferroxidase that plays important roles in cellular iron trafficking. Previous findings suggest that the proper regulation and subcellular localization of iron are very important in brain cell function and viability. Brain iron dyshomeostasis is observed during normal aging, as well as in several neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, coincident with areas more susceptible to insults. Because of their high metabolic demand and electrical excitability, neurons are particularly vulnerable to ischemic injury and death. We therefore set out to look for abnormalities in the brain of young adult mice that lack Cp. We found that iron levels in the striatum and cerebral cortex of these young animals are significantly lower than wild-type (WT) controls. Also mRNA levels of the neurotrophin brain derived neurotrophic factor (BDNF), known for its role in maintenance of cell viability, were decreased in these brain areas. Chelator-mediated depletion of iron in cultured neural cells resulted in reduced BDNF expression by a posttranscriptional mechanism, suggesting a causal link between low brain iron levels and reduced BDNF expression. When the mice were subjected to middle cerebral artery occlusion, a model of focal ischemic stroke, we found increased brain damage in Cp-deficient mice compared to WT controls. Our data indicate that lack of Cp increases neuronal susceptibility to ischemic injury by a mechanism that may involve reduced levels of iron and BDNF

Lunar Mare Basaltic Volcanism : Volcanic Features and Emplacement Processes

Volcanism is a fundamental process in the geological evolution of the Moon, providing clues to the composition and structure of the mantle, the location and duration of interior melting, the nature of convection and lunar thermal evolution. Progress in understanding volcanism has been remarkable in the short 60-year span of the Space Age. Before Sputnik 1 in 1957, the lunar farside was unknown, the origin of the dark lunar maria was debated (sedimentary or volcanic), and significant controversy surrounded the question of how the multitude of craters on the surface formed

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Patricia Moore : Paintings

Moore's abstract paintings are related to her interest in gesture, sensitive color relations and movement. Biographical notes

Three From P.E.I.

Brief presentation of three artists from Prince Edward Island accompanied by artists' statements. Biographical notes

Mission Concept and Design for the Orbiting Aerosol Observatory

Preliminary design and analysis has been performed for a 6U CubeSat to carry a miniaturized aerosol polarimetry sensor in order to examine the effect of atmospheric aerosols on the Earth’s climate This hypothetical satellite, the Orbiting Aerosol Observatory, is intended to perform partial mission objectives of the Glory spacecraft, which experienced a launch failure in 2011. The Orbiting Aerosol Observatory will collect data on the types and concentrations of aerosols in the atmosphere by observing incident sunlight reflected from the oceans from a position within the Afternoon Constellation. Subsystem requirements and component selection will be discussed. The Orbiting Aerosol Observatory consists primarily of off-the-shelf components with prior flight heritage to minimize cost, accelerate development, and maximize reliability. A series of simulations were created in MATLAB, Simulink, and Systems Tool Kit to model the satellite’s operation in orbit and ensure propulsive, attitude determination and control, power, communications, and thermal systems could perform to the system requirements. Development, build, and test plans were created, and a budget was developed to project costs throughout the mission life cycle