The Context Camera (CTX) on the Mars Reconnaissance Orbiter (MRO) is a Facility Instrument (i.e., government‐furnished equipment operated by a science team not responsible for design and fabrication) ...designed, built, and operated by Malin Space Science Systems and the MRO Mars Color Imager team (MARCI). CTX will (1) provide context images for data acquired by other MRO instruments, (2) observe features of interest to NASA's Mars Exploration Program (e.g., candidate landing sites), and (3) conduct a scientific investigation, led by the MARCI team, of geologic, geomorphic, and meteorological processes on Mars. CTX consists of a digital electronics assembly; a 350 mm f/3.25 Schmidt‐type telescope of catadioptric optical design with a 5.7° field of view, providing a ∼30‐km‐wide swath from ∼290 km altitude; and a 5000‐element CCD with a band pass of 500–700 nm and 7 μm pixels, giving ∼6 m/pixel spatial resolution from MRO's nearly circular, nearly polar mapping orbit. Raw data are transferred to the MRO spacecraft flight computer for processing (e.g., data compression) before transmission to Earth. The ground data system and operations are based on 9 years of Mars Global Surveyor Mars Orbiter Camera on‐orbit experience. CTX has been allocated 12% of the total MRO data return, or about ≥3 terabits for the nominal mission. This data volume would cover ∼9% of Mars at 6 m/pixel, but overlapping images (for stereo, mosaics, and observation of changes and meteorological events) will reduce this area. CTX acquired its first (instrument checkout) images of Mars on 24 March 2006.
Accurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green ...fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers.
In this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed.
Between Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39–62; p<0·0001). In the modified intention-to-treat population (n=176), 545 nodes were identified, of which 513 (94%) were confirmed to be lymph nodes on pathological processing: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0·30). Nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. 495 (96%) of 513 nodes were identified with the green dye and 238 (46%) with the blue dye (50%, 39–61; p<0·0001).
Indocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances.
Novadaq.
The quantification and characterization of natural, engineered, and incidental nano- to micro-size particles are beneficial to assessing a nanomaterial’s performance in manufacturing, their fate and ...transport in the environment, and their potential risk to human health. Single particle inductively coupled plasma mass spectrometry (spICP-MS) can sensitively quantify the amount and size distribution of metallic nanoparticles suspended in aqueous matrices. To accurately obtain the nanoparticle size distribution, it is critical to have knowledge of the size detection limit (denoted as D min) using spICP-MS for a wide range of elements (other than a few available assessed ones) that have been or will be synthesized into engineered nanoparticles. Herein is described a method to estimate the size detection limit using spICP-MS and then apply it to nanoparticles composed of 40 different elements. The calculated D min values correspond well for a few of the elements with their detectable sizes that are available in the literature. Assuming each nanoparticle sample is composed of one element, D min values vary substantially among the 40 elements: Ta, U, Ir, Rh, Th, Ce, and Hf showed the lowest D min values, ≤10 nm; Bi, W, In, Pb, Pt, Ag, Au, Tl, Pd, Y, Ru, Cd, and Sb had D min in the range of 11–20 nm; D min values of Co, Sr, Sn, Zr, Ba, Te, Mo, Ni, V, Cu, Cr, Mg, Zn, Fe, Al, Li, and Ti were located at 21–80 nm; and Se, Ca, and Si showed high D min values, greater than 200 nm. A range of parameters that influence the D min, such as instrument sensitivity, nanoparticle density, and background noise, is demonstrated. It is observed that, when the background noise is low, the instrument sensitivity and nanoparticle density dominate the D min significantly. Approaches for reducing the D min, e.g., collision cell technology (CCT) and analyte isotope selection, are also discussed. To validate the D min estimation approach, size distributions for three engineered nanoparticle samples were obtained using spICP-MS. The use of this methodology confirms that the observed minimum detectable sizes are consistent with the calculated D min values. Overall, this work identifies the elements and nanoparticles to which current spICP-MS approaches can be applied, in order to enable quantification of very small nanoparticles at low concentrations in aqueous media.
The degree of T cell self-reactivity considered dangerous by the immune system, thereby requiring thymic selection processes to prevent autoimmunity, is unknown. Here, we analyzed a panel of T cell ...receptors (TCRs) with a broad range of reactivity to ovalbumin (OVA323-339) in the rat insulin promoter (RIP)-mOVA self-antigen model for their ability to trigger thymic self-tolerance mechanisms. Thymic regulatory T (Treg) cell generation in vivo was directly correlated with in vitro TCR reactivity to OVA-peptide in a broad ∼1,000-fold range. Interestingly, higher TCR affinity was associated with a larger Treg cell developmental “niche” size, even though the amount of antigen should remain constant. The TCR-reactivity threshold to elicit thymic negative selection and peripheral T cell responses was ∼100-fold higher than that of Treg cell differentiation. Thus, these data suggest that the broad range of self-reactivity that elicits thymic Treg cell generation is tuned to secure peripheral tolerance to self.
► Treg cell development is correlated with self-reactivity over a broad range ► Foreign antigen reactive Treg cells may be generated by cross-reactivity to self ► TCR affinity is correlated with the size of the Treg cell developmental “niche” ► Peripheral responses need greater self-reactivity than thymic Treg cell selection
Excessive and prolonged activity of inflammatory monocytes is a hallmark of many diseases with an inflammatory component. In such conditions, precise targeting of these cells could be therapeutically ...beneficial while sparing many essential functions of the innate immune system, thus limiting unwanted effects. Inflammatory monocytes-but not the noninflammatory subset-depend on the chemokine receptor CCR2 for localization to injured tissue. Here we present an optimized lipid nanoparticle and a CCR2-silencing short interfering RNA that, when administered systemically in mice, show rapid blood clearance, accumulate in spleen and bone marrow, and localize to monocytes. Efficient degradation of CCR2 mRNA in monocytes prevents their accumulation in sites of inflammation. Specifically, the treatment attenuates their number in atherosclerotic plaques, reduces infarct size after coronary artery occlusion, prolongs normoglycemia in diabetic mice after pancreatic islet transplantation, and results in reduced tumor volumes and lower numbers of tumor-associated macrophages.
Several lines of evidence indicate that the advent of oxygenic photosynthesis preceded the oxygenation of the atmosphere—perhaps by as much as 300million years. The fate of biogenic O2 prior to its ...appearance in the atmosphere remains speculative, but recent work suggests that O2 was locally available within the surface ocean to support aerobic microbial ecosystems. Simple mass balance predicts that locally oxygenated environments (oxygen oases) could exist in areas of high productivity if the local rate of O2 production by oxygenic photosynthesis exceeded the combined rate of O2 loss by a number of processes (e.g., exchange with the atmosphere, transport within the ocean, reaction with reduced aqueous species, biological consumption). The areal extent of these environments and the dissolved O2 concentrations that could have persisted in an otherwise anoxic ocean, however, are key uncertainties in our understanding of the spatiotemporal redox-evolution of the early earth system.
We use an earth system model of intermediate complexity that has been modified to simulate a theoretical Archean biosphere in order to explore redox heterogeneity in the late Archean surface ocean. We demonstrate that oxygen oases are an expected consequence of oxygenic photosynthesis beneath an essentially O2-devoid atmosphere—and that oxygenated surface waters need not be restricted to shallow coastal environments or microbial mats. Within oxygen oases, O2 concentrations locally approach ~1–10μM for a large range of plausible Archean conditions. Although O2 concentrations in the open ocean are exceedingly low, biologically relevant dissolved O2 concentrations are widespread in our hypothetical surface ocean.
•Oxygenic photosynthesis generates oxygen oases under late Archean conditions.•Oxygen oases are large-scale, steady state features of the pelagic surface ocean.•Up to ~1–10μM O2 is possible locally in an otherwise essentially anoxic world.•Aerobic metabolism could have been widespread in a broadly anoxic Archean ocean.
Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis. Using RNA-seq profiling of the intima of lesions, here we identify a ...macrophage-specific lncRNA MAARS (Macrophage-Associated Atherosclerosis lncRNA Sequence). Aortic intima expression of MAARS increases by 270-fold with atherosclerotic progression and decreases with regression by 60%. MAARS knockdown reduces atherosclerotic lesion formation by 52% in LDLR
mice, largely independent of effects on lipid profile and inflammation, but rather by decreasing macrophage apoptosis and increasing efferocytosis in the vessel wall. MAARS interacts with HuR/ELAVL1, an RNA-binding protein and important regulator of apoptosis. Overexpression and knockdown studies verified MAARS as a critical regulator of macrophage apoptosis and efferocytosis in vitro, in an HuR-dependent manner. Mechanistically, MAARS knockdown alters HuR cytosolic shuttling, regulating HuR targets such as p53, p27, Caspase-9, and BCL2. These findings establish a mechanism by which a macrophage-specific lncRNA interacting with HuR regulates apoptosis, with implications for a broad range of vascular disease states.
Research examining the association between environmental attributes and physical activity among youth is growing. An updated review of literature is needed to summarize the current evidence base, and ...to inform policies and environmental interventions to promote active lifestyles among young people.
A literature search was conducted using the Active Living Research (ALR) literature database, an online database that codes study characteristics and results of published papers on built/social environment and physical activity/obesity/sedentary behavior. Papers in the ALR database were identified through PubMed, Web of Science, and SPORTDiscus using systematically developed and expert-validated search protocols. For the current review, additional inclusion criteria were used to select observational, quantitative studies among youth aged 3-18 years.
Papers were categorized by design features, sample characteristics, and measurement mode. Relevant results were summarized, stratified by age (children or adolescents) and mode of measurement (objective or perceived) for environmental attributes and physical activity. Percentage of significant results was calculated.
Mode of measurement greatly influenced the consistency of associations between environmental attributes and youth physical activity. For both children and adolescents, the most consistent associations involved objectively measured environmental attributes and reported physical activity. The most supported correlates for children were walkability, traffic speed/volume, access/proximity to recreation facilities, land-use mix, and residential density. The most supported correlates for adolescents were land-use mix and residential density. These findings support several recommendations for policy and environmental change from such groups as the IOM and National Physical Activity Plan.
The aim of this study was to compare the incidence of skin and soft tissue infections (SSTIs) across healthcare settings and analyze direct healthcare expenditures related to SSTIs in 2000 and 2012 ...in the United States.
We performed a retrospective, cross-sectional analysis of nationally representative data from the Medical Expenditure Panel Surveys. Population-based incidence rates were examined for all healthcare settings that include inpatient visits, emergency department visits and ambulatory visits for SSTIs. The direct costs of healthcare services utilization were reported. Population-based prescribing rates for each antimicrobial class during ambulatory visits were compared.
A total of 2.4 million patients experienced an SSTI in 2000 compared to 3.3 million in 2012 (40% increase). From 2000 to 2012, the incidence of patients with at least one hospital visit for SSTIs increased 22%, ambulatory care visits increased 30%, and emergency department visits increased 40%. The incidence of SSTIs in children and adolescents declined 50% (from 150 to 76 per 10,000 person; RR = 0.51, 95% CI: 0.38-0.67; p<0.001) whereas SSTIs in older adults (> 65 years of age) increased almost 2-fold (from 67 to 130 per 10,000 person; RR = 1.94, 95% CI: 1.44-2.61; p<0.001). The annual incidence of SSTI in adults did not change significantly from 2000 to 2012 (from 84 to 81 per 10,000 person; RR = 0.96, 95% CI: 0.71-1.31; p = 0.41). The total estimated direct healthcare costs of SSTIs increased 3-fold from $4.8 billion in 2000 to $15.0 billion in 2012, largely driven by an 8-fold increase in ambulatory expenditures for SSTIs. Total population-based antimicrobial prescription rates for SSTIs increased 4-fold from 2000 to 2012 (from 59.5 to 250.4 per 10,000 person).
The highest healthcare utilization for SSTI treatment occurred in the ambulatory care setting and also accounted for the largest increase in overall direct expenditures from 2000 to 2012.
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