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The BioCD is a spinning biochip that uses quadrature laser interferometry to detect captured protein on the disc surface. We describe the detection limits of protein binding on this optical biosensor. The fundamental metrology limit is 1 picometer for a single 100-micron diameter spot. Under assay conditions for prostate specific antigen, we can detect 25 pg/ml at 10 assays per disc.
Molecular interferometric imaging (MI2) is a label-free optical biosensor that combines common-path interferometry with shot-noise limited characteristics of a CCD array detector to detect protein binding to surfaces. In the metrology limit, it has achieved roughness-limited surface height resolution of 15 pm per 0.4 micron pixel, corresponding to a scaling mass sensitivity of 7 fg/mm, and a molecular resolution of about 15 IgG molecules per pixel. We have applied MI2 to detect cytokine interleukin-5 at a concentration detection limit of 50 pg/mL with a sandwich immunoassay. Real-time binding assays with MI2 enable the study of reaction kinetics, with a scaling mass sensitivity of 2 pg/mm under 7x magnification. Real-time MI2 measurements of anti-rabbit IgG against rabbit IgG were compared with results from surface plasmon resonance, with identical association rate constants at 5x103 M-1sec-1.
Introduction: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.
The introduction of agriculture is known to have profoundly affected the ecological complexion of landscapes. In this study, a rapid transition from C3 to C4 vegetation is inferred from a shift to higher stable carbon (13C/12C) isotope ratios of soils and sediments in the Benoué River Valley and upland Fali Mountains in northern Cameroon. Landscape change is viewed from the perspective of two settlement mounds and adjacent floodplains, as well as a rock terrace agricultural field dating from 1100 cal yr BP to the recent past (<400 cal yr BP). Nitrogen (15N/14N) isotope ratios and soil micromorphology demonstrate variable uses of land adjacent to the mound sites. These results indicate that Early Iron Age settlement practices involved exploitation of C3 plants on soils with low δ15N values, indicating wetter soils. Conversely, from the Late Iron Age (>700 cal yr BP) until recent times, high soil and sediment δ13C and δ15N values reflect more C4 biomass and anthropogenic organic matter in open, dry environments. The results suggest that Iron Age settlement practices profoundly changed landscapes in this part of West Africa through land clearance and/or utilization of C4 plants.
Employing atomic-scale simulations, the response of a high-angle grain boundary (GB), the soft/hard GB, against external loading was systematically investigated. Under tensile loading close to the hard orientation, strain-induced dynamic recrystallization was observed to initiate through direct soft-to-hard grain reorientation, which was triggered by stress mismatch, inhibited by surface tension from the soft-hard GB, and proceeded by interface ledges. Such grain reorientation corresponds with expansion and contraction of the hard grain along and perpendicular to the loading direction, respectively, accompanied by local atomic shuffling, providing relatively large normal strain of 8.3% with activation energy of 0.04 eV per atom. Tensile strain and residual dislocations on the hard/soft GB facilitate the initiation of dynamic recrystallization by lowering the energy barrier and the critical stress for grain reorientation, respectively.
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
Few studies have examined functional connectivity (FC) patterns using functional magnetic resonance imaging (fMRI) to predict outcomes in late-life depression. We hypothesized that FC within and between frontal and limbic regions would be associated with 12-week depression outcome in older depressed adults. Seventy-one subjects with major depression were enrolled in the study. A study geriatric psychiatrist performed a clinical interview and completed a Montgomery-Åsberg Depression Rating Scale (MADRS). All study participants were free of medication at baseline and had a brain fMRI scan. Using a regions of interest (ROI) atlas (including 164 ROIs), we conducted ROI-to-ROI resting-state FC analyses for each participant. In terms of treatment participants were offered sertraline initially, although in this naturalistic study, other medications were also prescribed. Subjects were evaluated every 2 weeks up to 12 weeks by the study psychiatrist, who followed a flexible, clinically based medication dosing schedule. Multivariate regression analysis was used to examine correlation between change of MADRS score over 12 weeks and baseline FC between brain regions, controlling for age, gender, mean head motion, and baseline MADRS. We found greater FC between the left inferior frontal gyrus pars triangularis and the left frontal eye field and FC of these two regions with a number of brain regions related to reward, salience, and sensorimortor function were correlated with change in MADRS score over 12 weeks. Our results highlight the important role of between inner speech-reward, attention-salience, and attention-sensorimotor network synchronization in predicting acute treatment response in late-life depression.
The flow of heat in materials is generally perceived to be a slow process and, therefore, pump-probe techniques originally developed for ultrafast time-resolved optical spectroscopy are not an obvious source of technologies for advances in thermal-property measurements. Nevertheless, over the past 18 years, the work of approximately 30 dedicated students and postdoctoral researchers at the University of Illinois at Urbana-Champaign has developed time-domain thermoreflectance (TDTR) into a nearly universal, high-throughput tool for measuring the thermal conductivity of materials and the thermal conductance of materials interfaces. This article illustrates the utility of TDTR and surveys current topics in the science of heat conduction in materials with recent examples drawn from high-thermal-conductivity crystals of cubic boron phosphide and boron arsenide, structure–property relationships for thermal conductivity of amorphous polymers, and thermal conductivity switching in liquid-crystal networks.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
To determine whether nut intake is associated with the prevalence of metabolic syndrome in US adolescents.
A cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) years 2003–2012. Anthropometric measurements, blood tests, 24 h diet recalls and demographic data were retrieved for participating adolescents. Metabolic syndrome was defined according to paediatric-modified Adult Treatment Panel III criteria. The exposure was defined as a nut intake ≥5 g/d.
Individuals aged 12–19 years (n 2805).
Nut consumption was associated with lower odds for metabolic syndrome (crude OR=0·25; 95 % CI 0·11, 0·55; P≤0·001). This effect was independent of age, sex, race/ethnicity and family income:poverty ratio (adjusted OR=0·27; 95 % CI 0·12, 0·61; P=0·002), and was stable after controlling for nutritional covariates including intake of sugar and total energy consumption (OR=0·36; 95 % CI 0·16, 0·81; P=0·014).
Nut consumption of ≥5 g/d is independently associated with lower odds for metabolic syndrome in US adolescents.
The influence of the content of trifluoroacetate (TFA), in the precursor solution, on the critical current density (Jc) of YBa2Cu3O7−x (YBCO) superconducting films was investigated. We found that a TFA/Ba ratio of 0.68 is optimal to obtain high-performance YBCO films. Using this optimal solution, we then developed an ultraviolet (UV) light soaking technique to prepare YBCO films. This resulted in the constituent elements being uniformly distributed in the films, and this then enabled enhanced Jc. The addition of water vapor during the UV soaking process decreased the content of carbon residue in the films, and further increased the Jc of the resulting YBCO films.