Metagenetic analysis of patterns of distribution and diversity of marine meiobenthic eukaryotes

AimMeiofaunal communities that inhabit the marine benthos offer unique opportunities to simultaneously study the macroecology of numerous phyla that exhibit different life-history strategies. Here, we ask: (1) if the macroecology of meiobenthic communities is explained mainly by dispersal constraints or by environmental conditions; and (2) if levels of meiofaunal diversity surpass existing estimates based on morphological taxonomy. LocationUK and mainland European coast. MethodsNext-generation sequencing techniques (NGS; Roche 454 FLX platform) using 18S nuclear small subunit ribosomal DNA (rDNA) gene. Pyrosequences were analysed using AmpliconNoise followed by chimera removal using Perseus. ResultsRarefaction curves revealed that sampling saturation was only reached at 15% of sites, highlighting that the bulk of meiofaunal diversity is yet to be discovered. Overall, 1353 OTUs were recovered and assigned to 23 different phyla. The majority of sampled sites had c. 60-70 unique operational taxonomic units (OTUs) per site, indicating high levels of beta diversity. The environmental parameters that best explained community structure were seawater temperature, geographical distance and sediment size, but most of the variability (R-2=70%-80%) remains unexplained. Main conclusionsHigh percentages of endemic OTUs suggest that meiobenthic community composition is partly niche-driven, as observed in larger organisms, but also shares macroecological features of microorganisms by showing high levels of cosmopolitanism (albeit on a much smaller scale). Meiobenthic communities exhibited patterns of isolation by distance as well as associations between niche, latitude and temperature, indicating that meiobenthic communities result from a combination of niche assembly and dispersal processes. Conversely, isolation-by-distance patterns were not identified in the featured protists, suggesting that animals and protists adhere to radically different macroecological processes, linked to life-history strategies.Natural Environment Research Council (NERC) [NE/E001505/1, NE/F001266/1, MGF-167]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/27413/2006, SFRH/BPD/80447/2014]; EPSRC [EP/H003851/1]; BBSRC CASE studentship; Unilever; Biotechnology and Biological Sciences Research Council [987347]; Engineering and Physical Sciences Research Council [EP/H003851/1]; Natural Environment Research Council [NE/F001290/1, NE/F001266/1, NE/E001505/1, NBAF010002]info:eu-repo/semantics/publishedVersio

High pretreatment disease burden as a risk factor for infectious complications following CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma

Infection has emerged as the chief cause of non‐relapse mortality (NRM) post CD19‐targeting chimeric antigen receptor T‐cell therapy (CAR‐T) therapy. Even though up to 50% of patients may remain infection‐free, many suffer multiple severe, life‐threatening, or fatal infectious events. The primary aim of this study was to explore severe and life‐threatening infections post licensed CAR‐T therapy in large B‐cell lymphoma, with a focus on the role of disease burden and disease sites in assessing individual risk. We sought to understand the cohort of patients who experience ≥2 infections and those at the highest risk of infectious NRM. Our analysis identifies a higher disease burden after bridging therapy as associated with infection events. Those developing ≥2 infections emerged as a uniquely high‐risk cohort, particularly if the second (or beyond) infection occurred during an episode of immune effector cell‐associated neurotoxicity syndrome (ICANS) or while on steroids and/or anakinra for ICANS. Herein, we also describe the first reported cases of “CAR‐T cold sepsis,” a phenomenon characterized by the lack of an appreciable systemic inflammatory response at the time of detection of infection. We propose a risk‐based strategy to encourage heightened clinician awareness of cold sepsis, with a view to reducing NRM

Pressure and Volume Limited Ventilation for the Ventilatory Management of Patients with Acute Lung Injury: A Systematic Review and Meta-Analysis

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses. Lung injury may be perpetuated by ventilation strategies that do not limit lung volumes and airway pressures. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pressure and volume-limited (PVL) ventilation strategies with more traditional mechanical ventilation in adults with ALI and ARDS.We searched Medline, EMBASE, HEALTHSTAR and CENTRAL, related articles on PubMed™, conference proceedings and bibliographies of identified articles for randomized trials comparing PVL ventilation with traditional approaches to ventilation in critically ill adults with ALI and ARDS. Two reviewers independently selected trials, assessed trial quality, and abstracted data. We identified ten trials (n = 1,749) meeting study inclusion criteria. Tidal volumes achieved in control groups were at the lower end of the traditional range of 10-15 mL/kg. We found a clinically important but borderline statistically significant reduction in hospital mortality with PVL [relative risk (RR) 0.84; 95% CI 0.70, 1.00; p = 0.05]. This reduction in risk was attenuated (RR 0.90; 95% CI 0.74, 1.09, p = 0.27) in a sensitivity analysis which excluded 2 trials that combined PVL with open-lung strategies and stopped early for benefit. We found no effect of PVL on barotrauma; however, use of paralytic agents increased significantly with PVL (RR 1.37; 95% CI, 1.04, 1.82; p = 0.03).This systematic review suggests that PVL strategies for mechanical ventilation in ALI and ARDS reduce mortality and are associated with increased use of paralytic agents

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Background The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods. Methods Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19–40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the ten-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes. Findings Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe. Interpretation Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression

Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of $ 7 Days of Mechanical Ventilation : Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study

Abstract : Background: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. Methods: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. Results: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). Conclusions: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders

Effects of variable magma supply on mid-ocean ridge eruptions : constraints from mapped lava flow fields along the Galápagos Spreading Center

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 13 (2012): Q08014, doi:10.1029/2012GC004163.Mapping and sampling of 18 eruptive units in two study areas along the Galápagos Spreading Center (GSC) provide insight into how magma supply affects mid-ocean ridge (MOR) volcanic eruptions. The two study areas have similar spreading rates (53 versus 55 mm/yr), but differ by 30% in the time-averaged rate of magma supply (0.3 × 106 versus 0.4 × 106 m3/yr/km). Detailed geologic maps of each study area incorporate observations of flow contacts and sediment thickness, in addition to sample petrology, geomagnetic paleointensity, and inferences from high-resolution bathymetry data. At the lower-magma-supply study area, eruptions typically produce irregularly shaped clusters of pillow mounds with total eruptive volumes ranging from 0.09 to 1.3 km3. At the higher-magma-supply study area, lava morphologies characteristic of higher effusion rates are more common, eruptions typically occur along elongated fissures, and eruptive volumes are an order of magnitude smaller (0.002–0.13 km3). At this site, glass MgO contents (2.7–8.4 wt. %) and corresponding liquidus temperatures are lower on average, and more variable, than those at the lower-magma-supply study area (6.2–9.1 wt. % MgO). The differences in eruptive volume, lava temperature, morphology, and inferred eruption rates observed between the two areas along the GSC are similar to those that have previously been related to variable spreading rates on the global MOR system. Importantly, the documentation of multiple sequences of eruptions at each study area, representing hundreds to thousands of years, provides constraints on the variability in eruptive style at a given magma supply and spreading rate.This work was supported by the National Science Foundation grants OCE08–49813, OCE08–50052, and OCE08– 49711.2013-02-2

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers

Positron emission tomography and magnetic resonance imaging methods and datasets within the dominantly inherited Alzheimer network (DIAN)

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case–control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual’s point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of ‘sporadic’ AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers

CfA3: 185 Type Ia Supernova Light Curves from the CfA

We present multi-band photometry of 185 type-Ia supernovae (SN Ia), with over 11500 observations. These were acquired between 2001 and 2008 at the F. L. Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics (CfA). This sample contains the largest number of homogeneously-observed and reduced nearby SN Ia (z < 0.08) published to date. It more than doubles the nearby sample, bringing SN Ia cosmology to the point where systematic uncertainties dominate. Our natural system photometry has a precision of 0.02 mag or better in BVRIr'i' and roughly 0.04 mag in U for points brighter than 17.5 mag. We also estimate a systematic uncertainty of 0.03 mag in our SN Ia standard system BVRIr'i' photometry and 0.07 mag for U. Comparisons of our standard system photometry with published SN Ia light curves and comparison stars, where available for the same SN, reveal agreement at the level of a few hundredths mag in most cases. We find that 1991bg-like SN Ia are sufficiently distinct from other SN Ia in their color and light-curve-shape/luminosity relation that they should be treated separately in light-curve/distance fitter training samples. The CfA3 sample will contribute to the development of better light-curve/distance fitters, particularly in the few dozen cases where near-infrared photometry has been obtained and, together, can help disentangle host-galaxy reddening from intrinsic supernova color, reducing the systematic uncertainty in SN Ia distances due to dust.Comment: Accepted to the Astrophysical Journal. Minor changes from last version. Light curves, comparison star photometry, and passband tables are available at http://www.cfa.harvard.edu/supernova/CfA3