AIM: The objectives of this study are: (1) to study the relation between body mass index (BMI), percentage-weight-for-height (PWH) and percentage body fat (PBF) in Singaporean Chinese children; (2) ...to assess the applicability of an international definition of obesity (the International Obesity Task Force (IOTF) BMI) as a screening tool to detect childhood obesity, as compared with the current Singapore population-specific definition using PWH. METHODS: A total of 623 Chinese children aged 6-11 y (321 males, 302 females) were recruited from a school by proportionate (40%) stratified random sampling. BMI and PWH were calculated from weight and height, while PBF was derived using leg-to-leg bioelectrical impedance analysis. The strength of association among the three indices of obesity was assessed using Spearman's correlation coefficient. Obese children were defined as those above the 95th percentile of PBF in each age-gender-specific group. Sensitivity and specificity of IOTF-BMI cutoff values and PWH cutoff values were compared by testing their ability to correctly identify obese children. RESULTS: All three indices correlated well with one another (BMI:PWH r=0.83, BMI:PBF r=0.87, PWH:PBF r=0.76). Prevalence of obesity was lower using IOTF-BMI cutoffs (6.9%) than using PWH cutoffs (16.4%). The sensitivity and specificity of IOTF-BMI cutoff values were 75.0 and 96.0%, respectively, with sensitivity differing between boys (83.3%) and girls (66.6%) (P=0.35). In comparison, PWH cutoff values had higher sensitivity (91.6%) but lower specificity (86.6%), with no significant difference between the genders. CONCLUSION: IOTF-recommended BMI cutoff values had low sensitivity and may underestimate the local prevalence of childhood obesity. For screening purposes, we recommend that population-specific measures rather than international cutoff values be used.
Beta-amyloid (Abeta) plaques are the hallmark of Alzheimer disease (AD). A PET imaging tracer that binds to Abeta plaques in vivo, N-methyl-(11)C2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or ...(11)CPIB for "Pittsburgh Compound-B"), has significantly higher binding in subjects diagnosed with dementia of the Alzheimer type (DAT) compared to nondemented controls. The authors used this imaging technique to investigate whether abnormal binding occurs in clinically normal individuals, prior to the development of cognitive changes.
Forty-one nondemented subjects (age range 20 to 86 years) and 10 patients with DAT (age range 66 to 86 years) underwent (11)CPIB PET scanning. Regions of interest were drawn on the MRI over the cerebellar, prefrontal, lateral temporal, occipital, gyrus rectus, precuneus, and striatal cortex. Binding potential values (BPs), proportional to the density of (11)CPIB-Abeta binding sites, were calculated using the Logan graphical analysis and the cerebellar cortex for a reference tissue.
Patients with DAT had elevated BP values vs nondemented subjects (p < 0.0001). Four of the 41 nondemented subjects had elevated cortical BP values and their BP values as a group were not significantly different from the DAT subjects' BP values. Two of these four nondemented subjects had (11)CPIB uptake, both visually and quantitatively, that was indistinguishable from the DAT subjects.
Elevated (11)CPIB binding in nondemented subjects suggests that (11)CPIB amyloid imaging may be sensitive for detection of a preclinical Alzheimer disease state. Longitudinal studies will be required to determine the association of elevated (11)CPIB binding and risk of developing dementia of the Alzheimer type.
The approval of bedaquiline has placed energy metabolism in the limelight as an attractive target space for tuberculosis antibiotic development. While bedaquiline inhibits the mycobacterial F1F0 ATP ...synthase, small molecules targeting other components of the oxidative phosphorylation pathway have been identified. Of particular interest is Telacebec (Q203), a phase 2 drug candidate inhibitor of the cytochrome bcc:aa3 terminal oxidase. A functional redundancy between the cytochrome bcc:aa3 and the cytochrome bd oxidase protects M. tuberculosis from Q203‐induced death, highlighting the attractiveness of the bd‐type terminal oxidase for drug development. Here, we employed a facile whole‐cell screen approach to identify the cytochrome bd inhibitor ND‐011992. Although ND‐011992 is ineffective on its own, it inhibits respiration and ATP homeostasis in combination with Q203. The drug combination was bactericidal against replicating and antibiotic‐tolerant, non‐replicating mycobacteria, and increased efficacy relative to that of a single drug in a mouse model. These findings suggest that a cytochrome bd oxidase inhibitor will add value to a drug combination targeting oxidative phosphorylation for tuberculosis treatment.
Synopsis
The functional redundancy of two terminal oxidases in mycobacteria limits the efficacy of phase 2 clinical candidate Telacebec (Q203). In this study we identified a cytochrome bd oxidase inhibitor ND‐011992 that together with Q203 forms a bactericidal drug combination against Mycobacterium tuberculosis.
ND‐011992 was identified and validated as an inhibitor of the Cytochrome bd oxidase.
ND‐011992 and Q203 jointly enhanced inhibition of oxygen respiration, intracellular ATP depletion, and bactericidal activity.
The drug combination was active against M. tuberculosis clinical isolates of various lineages as well as against MDR‐ and XDR‐TB isolates.
The addition of ND‐011992 to Q203 treatment did not significantly alter the frequency of resistance to treatment, suggesting there is limited added risk of rapid emergence of escape mutants.
The ND‐011992‐Q203 combination showed enhanced killing effect in the animal study compared to that of single drugs, demonstrating translatability in an in vivo model.
The functional redundancy of two terminal oxidases in mycobacteria limits the efficacy of phase 2 clinical candidate Telacebec (Q203). In this study we identified a cytochrome bd oxidase inhibitor ND‐011992 that together with Q203 forms a bactericidal drug combination against Mycobacterium tuberculosis.
Circulating tumor cells (CTCs) may have utility as surrogate biomarkers and "virtual" biopsies. We report the clinical significance and molecular characteristics of CTCs and CTC clusters, termed ...circulating tumor microemboli (CTM), detected in patients with small-cell lung cancer (SCLC) undergoing standard treatment.
Serial blood samples from 97 patients receiving chemotherapy were analyzed using EpCam-based immunomagnetic detection and a filtration-based technique. Proliferation status (Ki67) and apoptotic morphology were examined. Associations of CTC and CTM number with clinical factors and prognosis were determined.
CTCs were present in 85% of patients (77 of 97 patients) and were abundant (mean ± standard deviation = 1,589 ± 5,565). CTM and apoptotic CTCs were correlated with total CTC number and were detected in 32% and 57% of patients, respectively. Pretreatment CTCs, change in CTC number after one cycle of chemotherapy, CTM, and apoptotic CTCs were independent prognostic factors. Overall survival was 5.4 months for patients with ≥ 50 CTCs/7.5 mL of blood and 11.5 months (P < .0001) for patients with less than 50 CTCs/7.5 mL of blood before chemotherapy (hazard ratio = 2.45; 95% CI, 1.39 to 4.30; P = .002). Subpopulations of apoptotic and of proliferating solitary CTCs were detected, whereas neither were observed within cell clusters (CTM), implicating both protection from anoikis and relative resistance to cytotoxic drugs for cells within CTM.
Both baseline CTC number and change in CTC number after one cycle of chemotherapy are independent prognostic factors for SCLC. Molecular comparison of CTCs to cells in CTM may provide novel insights into SCLC biology.
Opsite (Smith & Nephew, Hull, UK) is widely used in wound care but its use in eye protection against corneal abrasion during major surgery is rarely reported. The purpose of the current study is to ...compare the effectiveness of using Opsite in eye protection with either wet gauze alone or with wet gauze following application of eye ointment in patients undergoing living donor liver transplantation (LDLT).
This is a prospective, double-blinded, randomized controlled trial. Forty-one patients undergoing liver transplantation were enrolled. One eye of each patient was protected with sterile gauze soaked with normal saline solution and covered with Opsite. Duratears (ALCON, Fort Worth, Tex, United States) ointment was applied to the other eye before covering it with sterile wet gauze and Opsite (ointment group). The corneal examination was carried out after fluorescein staining before and at the end of surgery by the same doctor. A Student t-test and a χ2 test were used for the statistical analyses.
Forty-one patients with 82 eyes were observed in this study. No corneal epithelial defects were found in either the normal saline group or the ointment group.
Opsite combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing LDLT.
•Corneal epithelial defects during general anesthesia (GA) are common, occurring in about 42% of unprotected eyes.•The incidence of such defects occurring during GA drastically decreases from 44% in unprotected eyes to 2.1% in protected eyes.•Our method of using Opsite (Smith & Nephew, Hull, UK) combined with wet gauze with or without additional eye ointment provided 100% protection against corneal abrasion in patients undergoing living donor liver transplantation.
Aims. We study the environmental dependence of local luminous infrared galaxies (LIRGs) and ultraluminous infrared galaxies (ULIRGs) found in the Sloan Digital Sky Survey (SDSS) data. Methods. The ...LIRG and ULIRG samples are constructed by cross-correlating spectroscopic catalogs of galaxies of the SDSS Data Release 7 and the Infrared Astronomical Satellite Faint Source Catalog. We examine the effects of the large-scale background density (Σ5), galaxy clusters and the nearest neighbor galaxy on the properties of infrared galaxies (IRGs). Results. We find that the fraction of LIRGs plus ULIRGs among IRGs (f(U)LIRGs) and the infrared luminosity (LIR) of IRGs strongly depend on the morphology of and the distance to the nearest neighbor galaxy: the probability of an IRG being a (U)LIRG (f(U)LIRGs) and its LIR both increases as it approaches a late-type galaxy, but decreases as it approaches an early-type galaxy (within half the virial radius of its neighbor). We find no dependence of f(U)LIRGs on the background density (surface galaxy number density) at a fixed stellar mass of galaxies. The dependence of f(U)LIRGs on the distance to galaxy clusters is also found to be very weak, but in the highest density regions, such as the center of galaxy clusters, few (U)LIRGs are found. Conclusions. This environmental dependence of LIRGs and ULIRGs and the evolution of the star formation rate (SFR)-environment relation from high redshifts to low redshifts seem to support the idea that galaxy-galaxy interactions and merging play a critical role in triggering the star formation activity of LIRGs and ULIRGs.
Wet deposition is the dominant mechanism for removing black carbon (BC) from the atmosphere and is key in determining its atmospheric lifetime, vertical gradient and global transport. Despite the ...importance of BC in the climate system, especially in terms of its ability to modulate the radiative energy budget, there are few quantitative case studies of wet removal in ambient environments. We present a case study of BC wet removal by examining aerosol size distributions and BC coating properties sampled in three Canadian boreal biomass burning plumes, one of which passed through a precipitating cloud. This depleted the majority of the plume's BC mass, and the largest and most coated BC-containing particles were found to be preferentially removed, suggesting that nucleation scavenging was likely the dominant mechanism. Calculated single-scattering albedo (SSA) showed little variation, as a large number of non-BC particles were also present in the precipitation-affected plume. The remaining BC cores were smaller than those observed in previous studies of BC in post-precipitation outflow over Asia, possibly due to the thick coating by hydrophilic compounds associated with the Canadian biomass burning particles. This study provides measurements of BC size, mixing state and removal efficiency to constrain model parameterisations of BC wet removal in biomass burning regions, which will help to reduce uncertainty in radiative forcing calculations.
Summary
The North Wyke Farm Platform was established as a United Kingdom national capability for collaborative research, training and knowledge exchange in agro‐environmental sciences. Its remit is ...to research agricultural productivity and ecosystem responses to different management practices for beef and sheep production in lowland grasslands. A system based on permanent pasture was implemented on three 21‐ha farmlets to obtain baseline data on hydrology, nutrient cycling and productivity for 2 years. Since then two farmlets have been modified by either (i) planned reseeding with grasses that have been bred for enhanced sugar content or deep‐rooting traits or (ii) sowing grass and legume mixtures to reduce nitrogen fertilizer inputs. The quantities of nutrients that enter, cycle within and leave the farmlets were evaluated with data recorded from sensor technologies coupled with more traditional field study methods. We demonstrate the potential of the farm platform approach with a case study in which we investigate the effects of the weather, field topography and farm management activity on surface runoff and associated pollutant or nutrient loss from soil. We have the opportunity to do a full nutrient cycling analysis, taking account of nutrient transformations in soil, and flows to water and losses to air. The NWFP monitoring system is unique in both scale and scope for a managed land‐based capability that brings together several technologies that allow the effect of temperate grassland farming systems on soil moisture levels, runoff and associated water quality dynamics to be studied in detail.
Highlights
Can meat production systems be developed that are productive yet minimize losses to the environment?
The data are from an intensively instrumented capability, which is globally unique and topical.
We use sensing technologies and surveys to show the effect of pasture renewal on nutrient losses.
Platforms provide evidence of the effect of meteorology, topography and farm activity on nutrient loss.
We construct the first comprehensive radioactive background model for a dark matter search with charge-coupled devices (CCDs). We leverage the well-characterized depth and energy resolution of the ...DAMIC at SNOLAB detector and a detailed geant4-based particle-transport simulation to model both bulk and surface backgrounds from natural radioactivity down to 50 eVee . We fit to the energy and depth distributions of the observed ionization events to differentiate and constrain possible background sources, for example, bulk H 3 from silicon cosmogenic activation and surface Pb210 from radon plate-out. We observe the bulk background rate of the DAMIC at SNOLAB CCDs to be as low as 3.1±0.6 countskg-1day-1 keVee-1 , making it the most sensitive silicon dark matter detector. Finally, we discuss the properties of a statistically significant excess of events over the background model with energies below 200 eVee .
ABSTRACT We report on the mass and distance measurements of two single-lens events from the 2015 Spitzer microlensing campaign. With both finite-source effect and microlens parallax measurements, we ...find that the lens of OGLE-2015-BLG-1268 is very likely a brown dwarf (BD). Assuming that the source star lies behind the same amount of dust as the Bulge red clump, we find the lens is a 45 7 BD at 5.9 1.0 kpc. The lens of of the second event, OGLE-2015-BLG-0763, is a 0.50 0.04 star at 6.9 1.0 kpc. We show that the probability to definitively measure the mass of isolated microlenses is dramatically increased once simultaneous ground- and space-based observations are conducted.
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