Biomedical optical sensing using nano-/micro-structured metamaterials

Work on optical sensing techniques continues to advance - and optical sensing techniques and related technologies are becoming a well-established approach for, inter alia, applications in biomedical and environmental sensing. Both structured surfaces and arrays of integrated devices that are fabricated by means of classical planar technologies are likely to have a central role in the development of low-cost and reliable biosensors, at both the molecular and cell levels. One approach that has been demonstrated as viable in biomedical sensing is the use of fluorescent labelling, e.g. for carrying out competition immunoassays to identify the possible presence of specific analyte molecules in suitably prepared fluid samples. Many bio-materials exhibit a finite level of fluorescence that could possibly be exploited in sensing, but is also potentially problematic when it forms an undesired background, thereby limiting sensitivity. But the alternative approach of label-free biomedical sensing seems likely to be favoured in future applications. A 'standard' approach to label-free sensing exploits the detection of changes in the (complex) refractive index that occur when bio-material is added to the local environment of a designed resonant structure, thereby changing its resonance frequency. Designed tuning of reflection, transmission and absorption resonances can be used to help identify specific molecules, through selection of the known bond resonances of the molecules of interest. Since it is typically possible to organise resonant structures in arrays that consist of thousands of individual resonant 'atoms', thereby forming a metasurface, it has become possible to select and quantify various characteristic molecular bond resonances simultaneously - and to identify possible molecular compositions in composite bio-material

Potential for Supernova Neutrino Detection in MiniBooNE

The MiniBooNE detector at Fermilab is designed to search for $\nu_\mu \to \nu_e$ oscillation appearance at $E_\nu \sim 1 {\rm GeV}$ and to make a decisive test of the LSND signal. The main detector (inside a veto shield) is a spherical volume containing 0.680 ktons of mineral oil. This inner volume, viewed by 1280 phototubes, is primarily a \v{C}erenkov medium, as the scintillation yield is low. The entire detector is under a 3 m earth overburden. Though the detector is not optimized for low-energy (tens of MeV) events, and the cosmic-ray muon rate is high (10 kHz), we show that MiniBooNE can function as a useful supernova neutrino detector. Simple trigger-level cuts can greatly reduce the backgrounds due to cosmic-ray muons. For a canonical Galactic supernova at 10 kpc, about 190 supernova $\bar{\nu}_e + p \to e^+ + n$ events would be detected. By adding MiniBooNE to the international network of supernova detectors, the possibility of a supernova being missed would be reduced. Additionally, the paths of the supernova neutrinos through Earth will be different for MiniBooNE and other detectors, thus allowing tests of matter-affected mixing effects on the neutrino signal.Comment: Added references, version to appear in PR

Regulation of markers of synaptic function in mouse models of depression: chronic mild stress and decreased expression of VGLUT1

Depression has been linked to failure in synaptic plasticity originating from environmental and/or genetic risk factors. The chronic mild stress (CMS) model regulates the expression of synaptic markers of neurotransmitter function and associated depressive-like behaviour. Moreover, mice heterozygous for the synaptic vesicle protein (SVP) vesicular glutamate transporter 1 (VGLUT1), have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour. Here, we aimed to identify, in these two experimental models, mechanisms of failure in synaptic plasticity, common to stress and impaired glutamate function. First, we show that CMS induced a transient decrease of different plasticity markers (VGLUT1, synapsin 1, sinaptophysin, rab3A and activity regulated cytoskeletal protein Arc) but a long-lasting decrease of the brain derived neurotrophic factor (BDNF) as well as depressive-like behaviour. The immediate early gene (IEG) Arc was also downregulated in VGLUT1+/- heterozygous mice. In contrast, an opposite regulation of synapsin 1 was observed. Finally, both models showed a marked increase of cortical Arc response to novelty. Increased Arc response to novelty could be suggested as a molecular mechanism underlying failure to adapt to environmental changes, common to chronic stress and altered glutamate function. Further studies should investigate whether these changes are associated to depressive-like behaviour both in animal models and in depressed patients

Reflexive adaptation for resilient water services: lessons for theory and practice

‘Adaptive management’ concern attempts to manage complex social-ecological and socio-technical systems in nimble ways to enhance their resilience. In this paper, three forms of adaptive management are identified, ‘scientific’ forms focused on collation of scientific data in response to management experiments, but more recent developments adding processes of collaboration as well as emphasising the need for reflexivity, that is, conscious processes of opening up debates to different perspectives and values. While reflexive adaptive management has been increasingly discussed in theory, there is a lack of examples of what its application means in practice. As a response, this paper examines an ‘Adaptive Planning Process’ (APP), seeking to apply reflexive adaptive management as a means to improve climate resilience in the UK water sector. The APP’s three inter linked workshops – Aspiration, Scenario and Roadmapping – were co-developed and trialled in a water utility. By describing and justifying the choices made in the development of the APP, the paper aims to reveal some of the challenges that arise when trying to design processes that achieve reflexive adaptation. The paper concludes that, if applied to planning for climate change, reflexive adaptation has the potential to explore multiple value positions, highlight different potential futures and acknowledge (and hence, partly address) power differentials, and therefore to offer the possibility of real change. On the basis of the trial, we argue that through tapping the depth and breadth of internal knowledge the APP process created the potential for decision making to be joined up across different parts of the utility, and hence offering new strategies and routes for addressing uncertainties and delivering more resilient water services

Viremia trajectories of HIV in HIV-positive women in the United States, 1994-2017

IMPORTANCE Viral suppression of HIV is an important treatment goal to decrease morbidity, mortality, and risk of transmission to others. OBJECTIVE To characterize longitudinal HIV viral load outcomes among women enrolled in the Women's Interagency HIV Study (WIHS). DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of HIV-positive women with semiannual study visits and a minimum of 5 follow-up visits was conducted from 1994 to 2017. The WIHS sites included in this analysis are in Brooklyn and Bronx, New York; Chicago, Illinois; San Francisco, California; andWashington, DC. MAIN OUTCOMES AND MEASURES Women were categorized into groups based on their probability of achieving viral load suppression below 200 copies/mL using logistic trajectory modeling. Multinomial regression analysis was used to identify factors associated with placement in the group with the highest probability of viremia. RESULTS At baseline, the mean (SD) age of the 1989 women was 36.9 (8.0) years, mean CD4+ T-lymphocyte count was 467/mm3, median (interquartile range) HIV RNA was 6200.0 (384.5-41 678.0) copies/mL, and 1305 women (65.6%) were African American. Three trajectory groups were identified with low (568 [28.6%]), intermediate (784 [39.4%]), and high (637 [32.0%]) probability of viremia above 200 copies/mL. The mean (SD) cumulative years of viral suppression were 18.7 (4.0) years, 12.2 (3.1) years, and 5.8 (2.9) years in the respective groups. Factors associated with high probability of viremia included younger age (odds ratio [OR]. 0.99; 95%CI, 0.98-0.99; P = .03), African American race (odds ratio [OR], 2.43; 95%CI, 1.75-3.37), P < .001), Hispanic race/ ethnicity (OR, 1.50; 95%CI, 1.03-2.19; P = .04), increased levels of depressive symptoms (OR, 1.17; 95%CI, 1.01-1.36; P = .03), drug use (OR, 1.23; 95%CI, 1.01-1.51; P = .04), lower CD4+ T-lymphocyte counts (OR, 95%CI, 0.82; 0.80-0.85; P < .001), and unstable housing (OR, 1.25, 95%CI, 1.03-1.50; P = .02). Between 2015 and 2017, 71.2%of women demonstrated sustained viral suppression: 89.6% (310 of 346) of those with lowviremia, 83.4%(346 of 415) with intermediate, and 35.2%(112 of 318) with high probability of viremia. CONCLUSIONS AND RELEVANCE This longitudinal approach suggested that the probability of viremia decreased substantially over time for most participants, including among women with earlier histories of incomplete viral suppression. The findings from this study suggest that continued efforts are needed to address mental health, social, behavioral and structural factors that were identified as associated with high probability of HIV viremia over time

Predicting substance use behavior among South African adolescents: The role of leisure experiences across time

Using seven waves of data, collected twice a year from the 8th through the 11th grades in a low-resource community in Cape Town, South Africa, we aimed to describe the developmental trends in three specific leisure experiences (leisure boredom, new leisure interests, and healthy leisure) and substance use (cigarettes, alcohol, and marijuana) behaviors and to investigate the ways in which changes in leisure experiences predict changes in substance use behaviors over time. Results indicated that adolescents’ substance use increased significantly across adolescence, but that leisure experiences remained fairly stable over time. We also found that adolescent leisure experiences predicted baseline substance use and that changes in leisure experiences predicted changes in substance use behaviors over time, with leisure boredom emerging as the most consistent and strongest predictor of alcohol, cigarette, and marijuana use. Implications for interventions that target time use and leisure experiences are discussed.Web of Scienc

Mushy Zone Morphology During Directional Solidification of Pb-5.8 Wt Pct Sb Alloy

The Pb-5.8 wt pet Sb alloy was directionally solidified with a positive thermal gradient of 140 K cm(-1) at a growth speed ranging from 0.8 to 30 mu m s(-1), and then it was quenched to retain the mushy zone morphology. The morphology of the mushy zone along its entire length has been characterized by using a serial sectioning and three-dimensional image reconstruction technique. Variation in the cellular/dendritic shape factor, hydraulic radius of the interdendritic region, and fraction solid along the mushy zone length has been studied. A comparison with predictions from theoretical models indicates that convection remarkably reduces the primary dendrite spacing while its influence on the dendrite tip radius is not as significant

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Some Consequences of Thermosolutal Convection: The Grain Structure of Castings

The essential principles of thermosolutal convection are outlined, and how convection provides a transport mechanism between the mushy region of a casting and the open bulk liquid is illustrated. The convective flow patterns which develop assist in heat exchange and macroscopic solute segregation during solidification; they also provide a mechanism for the transport of dendritic fragments from the mushy region into the bulk liquid. Surviving fragments become nuclei for equiaxed grains and so lead to blocking of the parental columnar, dendritic growth front from which they originated. The physical steps in such a sequence are considered and some experimental data are provided to support the argument

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types