Biosensors for the Rapid Detection of Cardiovascular Biomarkers of Vital Interest: Needs, Analysis and Perspectives.

We have previously surveyed a panel of 508 physicians from around the world about which biomarkers would be relevant if obtained in a very short time frame, corresponding to emergency situations (life-threatening or not). The biomarkers that emerged from this study were markers of cardiovascular disease: troponin, D-dimers, and brain natriuretic peptide (BNP). Cardiovascular disease is a group of disorders affecting the heart and blood vessels. At the intersection of medicine, basic research and engineering, biosensors that address the need for rapid biological analysis could find a place of choice in the hospital or primary care ecosystem. Rapid, reliable, and inexpensive analysis with a multi-marker approach, including machine learning analysis for patient risk analysis, could meet the demand of medical teams. The objective of this opinion review, proposed by a multidisciplinary team of experts (physicians, biologists, market access experts, and engineers), is to present cases where a rapid biological response is indeed valuable, to provide a short overview of current biosensor technologies for cardiac biomarkers designed for a short result time, and to discuss existing market access issues.

Relevant Biomarkers in Medical Practices: An Analysis of the Needs Addressed by an International Survey.

(1) Backround: Technological advances should foster gains in physicians' efficiency. For example, a reduction of the medical decision time can be enabled by faster biological tests. The main objective of this study was to collect responses from an international panel of physicians on their needs for biomarkers and also to convey the improvement in the outcome to be made possible by the potential development of fast diagnostic tests for these biomarkers. (2) Methods: we distributed a questionnaire on the Internet to physicians. (3) Results: 508 physicians participated in this survey. The mean age was 38 years. General practice and emergency medicine were heavily represented, with 95% CIs of 44% (39.78, 48.41) and 32% (27.84, 35.94)), respectively. The two most represented countries were France (95% CI: 74% (70.20, 77.83)) and the USA (95% CI: 11% (8.65, 14.18)). Ninety-eight percentages of the physicians thought that obtaining cited biomarkers more quickly would be beneficial to their practice and to patient's care. The main biomarkers of interest identified by our panel were troponin (95% CI: 51% (46.24, 54.94)), C-reactive protein (95% CI: 42% (38.03, 46.62)), D-dimer (95% CI: 29% (24.80, 32.68)), and brain natriuretic peptide (95% CI: 13% (10.25, 16.13)). (4) Conclusions: Our study highlights the real technological need for fast biomarker results, which could be provided by biosensors. The relevance of some answers such as troponin is questionable.

Natural Boron and 10B-Enriched Hexagonal Boron Nitride for High-Sensitivity Self-Biased Metal-Semiconductor-Metal Neutron Detectors.

Metal-semiconductor-metal (MSM) detectors based on Ti/Au and Ni/Au interdigitated structures were fabricated using 2.5 micrometer thick hexagonal boron nitride (h-BN) layer with both natural and 10B-enriched boron. Current-voltage (I-V) and current-time (I-t) curves of the fabricated detectors were recorded with (I N) and without (I d) neutron irradiation, allowing the determination of their sensitivity (S = (I N - I d)/I d = ΔI/I d). Natural and 10B-enriched h-BN detectors exhibited high neutron sensitivities of 233 and 367% at 0 V bias under a flux of 3 × 104 n/cm2/s, respectively. An imbalance in the distribution of filled traps between the two electric contacts could explain the self-biased operation of the MSM detectors. Neutron sensitivity is further enhanced with electrical biasing, reaching 316 and 1192% at 200 V and a flux of 3 × 104 n/cm2/s for natural and 10B-enriched h-BN detectors, respectively, with dark current as low as 2.5 pA at 200 V. The increased performance under bias has been attributed to a gain mechanism based on neutron-induced charge carrier trapping at the semiconductor/metal interface. The response of the MSM detectors under thermal neutron flux and bias voltages was linear. These results clearly indicate that the thin-film monocrystal BN MSM neutron detectors can be optimized to operate sensitively with the absence of external bias and generate stronger signal detection using 10B-enriched boron.

Effectiveness and Kinematic Analysis of Initial Step Patterns for Multidirectional Acceleration in Team and Racquet Sports.

The ability for quick multidirectional accelerations is crucial for athletic performance in team and racquet sports. So far, there has been little research dedicated to different initial step patterns usually applied by players. Therefore, the present study investigated the kinematic characteristics and effectiveness of the following step patterns: Jab Step (JS), Pivot Step (PS), Gravity Step (GS) and Counter Step (CS). Twenty-two male competitive team and racquet sport athletes completed maximum lateral accelerations utilizing the step patterns. Following familiarization with each step pattern, three 5 m sprints (5 m STs) into both directions (left & right) were completed. Sprint times, the translation of the center of mass (CoM) and joint angles were obtained using three-dimensional motion analysis. 5 m STs of the CS were faster compared to the GS and PS for both directions. A detailed distance-time analysis revealed that for shorter distances only the JS was faster than the GS. Regarding the sequence in which the maximum angular velocities (max. w → ) in the hip, the knee, and the ankle were reached during the push off, there was a proximal-to-distal sequence for the JS and the CS, but a distal-to proximal sequence for the GS and the PS. The results reveal that the JS and the CS are superior for accelerations towards the lateral direction. Specifically, they indicate that the JS is more suitable for covering very short distances and the CS is superior for covering further distances. In addition, the distal-to-proximal sequence of max. w → during the push-off in the GS and the PS might indicate lower kinematic efficiency.

Towards P-Type Conduction in Hexagonal Boron Nitride: Doping Study and Electrical Measurements Analysis of hBN/AlGaN Heterojunctions.

Reliable p-doped hexagonal boron nitride (h-BN) could enable wide bandgap optoelectronic devices such as deep ultra-violet light emitting diodes (UV LEDs), solar blind photodiodes and neutron detectors. We report the study of Mg in h-BN layers as well as Mg h-BN/AlGaN heterostructures. Mg incorporation in h-BN was studied under different biscyclopentadienyl-magnesium (Cp2Mg) molar flow rates. 2θ-ω x-ray diffraction scans clearly evidence a single peak, corresponding to the (002) reflection plane of h-BN with a full-width half maximum increasing with Mg incorporation in h-BN. For a large range of Cp2Mg molar flow rates, the surface of Mg doped h-BN layers exhibited characteristic pleats, confirming that Mg doped h-BN remains layered. Secondary ion mass spectrometry analysis showed Mg incorporation, up to 4 × 1018 /cm3 in h-BN. Electrical conductivity of Mg h-BN increased with increased Mg-doping. Heterostructures of Mg h-BN grown on n-type Al rich AlGaN (58% Al content) were made with the intent of forming a p-n heterojunction. The I-V characteristics revealed rectifying behavior for temperatures from 123 to 423 K. Under ultraviolet illumination, photocurrent was generated, as is typical for p-n diodes. C-V measurements evidence a built-in potential of 3.89 V. These encouraging results can indicate p-type behavior, opening a pathway for a new class of wide bandgap p-type layers.

Effectiveness of selective area growth using van der Waals h-BN layer for crack-free transfer of large-size III-N devices onto arbitrary substrates.

Selective Area van der Waals Epitaxy (SAVWE) of III-Nitride device has been proposed recently by our group as an enabling solution for h-BN-based device transfer. By using a patterned dielectric mask with openings slightly larger than device sizes, pick-and-place of discrete LEDs onto flexible substrates was achieved. A more detailed study is needed to understand the effect of this selective area growth on material quality, device performance and device transfer. Here we present a study performed on two types of LEDs (those grown on h-BN on patterned and unpatterned sapphire) from the epitaxial growth to device performance and thermal dissipation measurements before and after transfer. Millimeter-size LEDs were transferred to aluminum tape and to silicon substrates by van der Waals liquid capillary bonding. It is shown that patterned samples lead to a better material quality as well as improved electrical and optical device performances. In addition, patterned structures allowed for a much better transfer yield to silicon substrates than unpatterned structures. We demonstrate that SAVWE, combined with either transfer processes to soft or rigid substrates, offers an efficient, robust and low-cost heterogenous integration capability of large-size devices to silicon for photonic and electronic applications.

Control of the Mechanical Adhesion of III-V Materials Grown on Layered h-BN.

Hexagonal boron nitride (h-BN) can be used as a p-doped material in wide-bandgap optoelectronic heterostructures or as a release layer to allow lift-off of grown three-dimensional (3D) GaN-based devices. To date, there have been no studies of factors that lead to or prevent lift-off and/or spontaneous delamination of layers. Here, we report a unique approach of controlling the adhesion of this layered material, which can result in both desired lift-off layered h-BN and mechanically inseparable robust h-BN layers. This is accomplished by controlling the diffusion of Al atoms into h-BN from AlN buffers grown on h-BN/sapphire. We present evidence of Al diffusion into h-BN for AlN buffers grown at high temperatures compared to conventional-temperature AlN buffers. Further evidence that the Al content in BN controls lift-off is provided by comparison of two alloys, Al0.03B0.97N/sapphire and Al0.17B0.83N/sapphire. Moreover, we tested that management of Al diffusion controls the mechanical adhesion of high-electron-mobility transistor (HEMT) devices grown on AlN/h-BN/sapphire. The results extend the control of two-dimensional (2D)/3D hetero-epitaxy and bring h-BN closer to industrial application in optoelectronics.

Gas sensors boosted by two-dimensional h-BN enabled transfer on thin substrate foils: towards wearable and portable applications.

The transfer of GaN based gas sensors to foreign substrates provides a pathway to enhance sensor performance, lower the cost and extend the applications to wearable, mobile or disposable systems. The main keys to unlocking this pathway is to grow and fabricate the sensors on large h-BN surface and to transfer them to the flexible substrate without any degradation of the performances. In this work, we develop a new generation of AlGaN/GaN gas sensors with boosted performances on a low cost flexible substrate. We fabricate 2-inch wafer scale AlGaN/GaN gas sensors on sacrificial two-dimensional (2D) nano-layered h-BN without any delamination or cracks and subsequently transfer sensors to an acrylic surface on metallic foil. This technique results in a modification of relevant device properties, leading to a doubling of the sensitivity to NO2 gas and a response time that is more than 6 times faster than before transfer. This new approach for GaN-based sensor design opens new avenues for sensor improvement via transfer to more suitable substrates, and is promising for next-generation wearable and portable opto-electronic devices.

Flexible metal-semiconductor-metal device prototype on wafer-scale thick boron nitride layers grown by MOVPE.

Practical boron nitride (BN) detector applications will require uniform materials over large surface area and thick BN layers. To report important progress toward these technological requirements, 1~2.5 µm-thick BN layers were grown on 2-inch sapphire substrates by metal-organic vapor phase epitaxy (MOVPE). The structural and optical properties were carefully characterized and discussed. The thick layers exhibited strong band-edge absorption near 215 nm. A highly oriented two-dimensional h-BN structure was formed at the film/sapphire interface, which permitted an effective exfoliation of the thick BN film onto other adhesive supports. And this structure resulted in a metal-semiconductor-metal (MSM) device prototype fabricated on BN membrane delaminating from the substrate. MSM photodiode prototype showed low dark current of 2 nA under 100 V, and 100 ± 20% photoconductivity yield for deep UV light illumination. These wafer-scale MOVPE-grown thick BN layers present great potential for the development of deep UV photodetection applications, and even for flexible (opto-) electronics in the future.

Nanoselective area growth of defect-free thick indium-rich InGaN nanostructures on sacrificial ZnO templates.

Nanoselective area growth (NSAG) by metal organic vapor phase epitaxy of high-quality InGaN nanopyramids on GaN-coated ZnO/c-sapphire is reported. Nanopyramids grown on epitaxial low-temperature GaN-on-ZnO are uniform and appear to be single crystalline, as well as free of dislocations and V-pits. They are also indium-rich (with homogeneous 22% indium incorporation) and relatively thick (100 nm). These properties make them comparable to nanostructures grown on GaN and AlN/Si templates, in terms of crystallinity, quality, morphology, chemical composition and thickness. Moreover, the ability to selectively etch away the ZnO allows for the potential lift-off and transfer of the InGaN/GaN nanopyramids onto alternative substrates, e.g. cheaper and/or flexible. This technology offers an attractive alternative to NSAG on AlN/Si as a platform for the fabrication of high quality, thick and indium-rich InGaN monocrystals suitable for cheap, flexible and tunable light-emitting diodes.

Investigation of the Performance of HEMT-Based NO, NO2 and NH3 Exhaust Gas Sensors for Automotive Antipollution Systems.

We report improved sensitivity to NO, NO2 and NH3 gas with specially-designed AlGaN/GaN high electron mobility transistors (HEMT) that are suitable for operation in the harsh environment of diesel exhaust systems. The gate of the HEMT device is functionalized using a Pt catalyst for gas detection. We found that the performance of the sensors is enhanced at a temperature of 600 °C, and the measured sensitivity to 900 ppm-NO, 900 ppm-NO2 and 15 ppm-NH3 is 24%, 38.5% and 33%, respectively, at 600 °C. We also report dynamic response times as fast as 1 s for these three gases. Together, these results indicate that HEMT sensors could be used in a harsh environment with the ability to control an anti-pollution system in real time.

Spatio-Temporal Dimensions of Child Poverty in America, 1990-2010.

The persistence of childhood poverty in the United States, a wealthy and developed country, continues to pose both an analytical dilemma and public policy challenge, despite many decades of research and remedial policy implementation. In this paper, our goals are twofold, though our primary focus is methodological. We attempt both to examine the relationship between space, time, and previously established factors correlated with childhood poverty at the county level in the continental United States as well as to provide an empirical case study to demonstrate an underutilized methodological approach. We analyze a spatially consistent dataset built from the 1990 and 2000 U.S. Censuses, and the 2006-2010 American Community Survey. Our analytic approach includes cross-sectional spatial models to estimate the reproduction of poverty for each of the reference years as well as a fixed effects panel data model, to analyze change in child poverty over time. In addition, we estimate a full space-time interaction model, which adjusts for spatial and temporal variation in these data. These models reinforce our understanding of the strong regional persistence of childhood poverty in the U.S. over time and suggest that the factors impacting childhood poverty remain much the same today as they have in past decades.

Graphene quantum interference photodetector.

In this work, a graphene quantum interference (QI) photodetector was simulated in two regimes of operation. The structure consists of a graphene nanoribbon, Mach-Zehnder interferometer (MZI), which exhibits a strongly resonant transmission of electrons of specific energies. In the first regime of operation (that of a linear photodetector), low intensity light couples two resonant energy levels, resulting in scattering and differential transmission of current with an external quantum efficiency of up to 5.2%. In the second regime of operation, full current switching is caused by the phase decoherence of the current due to a strong photon flux in one or both of the interferometer arms in the same MZI structure. Graphene QI photodetectors have several distinct advantages: they are of very small size, they do not require p- and n-doped regions, and they exhibit a high external quantum efficiency.

Primary care availability and emergency department use by older adults: a population-based analysis.

OBJECTIVES: To assess the relationship between the number of primary care providers (PCPs) in an area and emergency department (ED) visits by older adults. DESIGN: Population-based cross-sectional observational study. SETTING: Nonfederal EDs in North Carolina in 2010. PARTICIPANTS: All older adults (n = 640,086) presenting to a nonfederal ED in North Carolina in 2010. MEASUREMENTS: The primary outcome was the number of ED visits by older adults in each ZIP code per 100 adults aged 65 and older living in that ZIP code. A secondary outcome was the number of ED visits not resulting in hospital admission per 100 older adults. The primary predictor variable was the number of PCPs per 100 older residents for each ZIP code. Covariates included those representing healthcare need (Medicare hospitalizations, nursing home beds), predisposing factors for healthcare use (race, education, population density of older adults), and enabling factors (distance to the nearest ED). RESULTS: In a multivariable regression model corrected for spatial clustering, ZIP code characteristics associated with ED visits included more hospitalizations by Medicare beneficiaries, more nursing home beds, and closer proximity to an ED. Number of PCPs per 100 older adult residents in each ZIP code was not associated with ED use, and the 95% confidence limit indicates at most a small effect of PCP availability on ED use. CONCLUSION: These findings suggest that primary care availability has at most a limited effect on ED use by older adults in North Carolina.

Spatial variation in poverty-generating processes: Child poverty in the United States.

This study builds on research demonstrating that sub-regions within the United States have different processes that abet poverty and that child poverty is spatially differentiated. We focus on the social attributes of the local area to assess what the geographic place represents in terms of social characteristics, namely racial/ethnic composition and economic structure, and to resolve apparent inconsistencies in poverty research. Using spatial regime and spatial error regression techniques to analyze county census data, we examine spatial differentiation in the relationships that generate child poverty. Our approach addresses the conceptual and technical aspects of spatial inequality. Results show that local-area processes are at play with implications for more nuanced theoretical models and anti-poverty policies that consider systematic differences in factors contributing to child poverty according to the racial/ethnic and economic contexts.

Full-band quantum-dynamical theory of saturation and four-wave mixing in graphene.

The linear and nonlinear optical response of graphene are studied within a quantum-mechanical, full-band, steady-state density-matrix model. This nonpurtabative method predicts the saturatable absorption and saturable four-wave mixing of graphene. The model includes τ(1) and τ(2) time constants that denote carrier relaxation and quantum decoherence, respectively. Fits to existing experimental data yield τ(2) < 1 fs due to carrier-carrier scattering. τ(1) is found to be on the timescale from 250 fs to 550 fs, showing agreement with experimental data obtained by differential transmission measurements.

Community-level HIV risk behaviors and HIV prevalence among women and men in Zimbabwe.

Most studies on HIV risk in sub-Saharan Africa focus on individual-level sociodemographic and behavioral correlates of risk. Only recently have researchers and programmers considered the context within which individuals live. This study uses the 2005-6 Zimbabwe Demographic and Health Survey to examine the correlation between the prevalence of HIV at the community level and the prevalence of HIV risk-taking behaviors. Results show that women and men living in communities with higher HIV prevalence in the opposite sex are at increased risk of HIV. In addition, rural women and men living in communities with greater premarital and nonmarital sex are at greater risk of HIV. Finally, HIV prevalence is higher among women and men living in urban areas with higher intimate partner violence. Programs should address community-level social norms that make high-risk behaviors acceptable and thus increase all women and men's risk of HIV, not just those engaged in high-risk behaviors.

Protection from annual flooding is correlated with increased cholera prevalence in Bangladesh: a zero-inflated regression analysis.

BACKGROUND: Alteration of natural or historical aquatic flows can have unintended consequences for regions where waterborne diseases are endemic and where the epidemiologic implications of such change are poorly understood. The implementation of flood protection measures for a portion of an intensely monitored population in Matlab, Bangladesh, allows us to examine whether cholera outcomes respond positively or negatively to measures designed to control river flooding. METHODS: Using a zero inflated negative binomial model, we examine how selected covariates can simultaneously account for household clusters reporting no cholera from those with positive counts as well as distinguishing residential areas with low counts from areas with high cholera counts. Our goal is to examine how residence within or outside a flood protected area interacts with the probability of cholera presence and the effect of flood protection on the magnitude of cholera prevalence. RESULTS: In Matlab, living in a household that is protected from annual monsoon flooding appears to have no significant effect on whether the household experiences cholera, net of other covariates. However, counter-intuitively, among households where cholera is reported, living within the flood protected region significantly increases the number of cholera cases. CONCLUSIONS: The construction of dams or other water impoundment strategies for economic or social motives can have profound and unanticipated consequences for waterborne disease. Our results indicate that the construction of a flood control structure in rural Bangladesh is correlated with an increase in cholera cases for residents protected from annual monsoon flooding. Such a finding requires attention from both the health community and from governments and non-governmental organizations involved in ongoing water management schemes.

Security of a discretely signaled continuous variable quantum key distribution protocol for high rate systems.

We propose a continuous variable based quantum key distribution protocol that makes use of discretely signaled coherent light and reverse error reconciliation. We present a rigorous security proof against collective attacks with realistic lossy, noisy quantum channels, imperfect detector efficiency, and detector electronic noise. This protocol is promising for convenient, high-speed operation at link distances up to 50 km with the use of post-selection.

A 24 km fiber-based discretely signaled continuous variable quantum key distribution system.

We report a continuous variable key distribution system that achieves a final secure key rate of 3.45 kilobits/s over a distance of 24.2 km of optical fiber. The protocol uses discrete signaling and post-selection to improve reconciliation speed and quantifies security by means of quantum state tomography. Polarization multiplexing and a frequency translation scheme permit transmission of a continuous wave local oscillator and suppression of noise from guided acoustic wave Brillouin scattering by more than 27 dB.