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Background: Clinical practice guidelines have been developed to assist healthcare practitioners in clinical decision making. Publication of clinical practice guidelines does not automatically lead to their uptake and barrier identification has been recognized as an important step in implementation planning. This study aimed at developing a questionnaire to identify perceived barriers for implementing the Dutch COPD guideline for physical therapists and its recommended measurement instruments. Methods: An overall questionnaire, based on two existing questionnaires, was constructed to identify barriers and facilitators for implementing the COPD guideline. The construct of the questionnaire was assessed in a cross-sectional study among 246 chest physical therapists. Factor analysis was conducted to explore underlying dimensions. Psychometric properties were analyzed using Cronbach’s alpha. Barriers and facilitators were assessed using descriptive statistics. Results: Some 139 physical therapists (57%) responded. Factor analysis revealed 4-factor and 5-factor solutions with an explained variance of 36% and 39% respectively. Cronbach’s alpha of the overall questionnaire was 0.90, and varied from 0.66 to 0.92 for the different factors. Underlying domains of the 5-factor solution were characterized as: attitude towards using measurement instruments, knowledge and skills of the physical therapist, applicability of the COPD guideline, required investment of time & money, and patient characteristics. Physical therapists showed a positive attitude toward using the COPD guideline. Main barriers for implementation were required time investment and financial constraints. Conclusions: The construct of the questionnaire revealed relevant underlying domains for the identification of barriers and facilitators for implementing the COPD guideline. The questionnaire allowed for tailoring to the target group and may be used across health care professionals as basis for in-depth analysis of barriers to specific recommendations in guidelines. The results of the questionnaire alone do not provide sufficient information to inform the development of an implementation strategy. The infrastructure for developing the guideline can be used for addressing key barriers by the guideline development group, using the questionnaire as well as in-depth analysis such as focus group interviews. Further development of methods for prospective identification of barriers and consequent tailoring of implementation interventions is required.

Tunneling junctions having the structure AgTS–S(CH2)n−1CH3//Ga2O3/EGaIn allow physical–organic studies of charge transport across self-assembled monolayers (SAMs). In ambient conditions, the surface of the liquid metal electrode (EGaIn, 75.5 wt % Ga, 24.5 wt % In, mp 15.7 °C) oxidizes and adsorbs―like other high-energy surfaces―adventitious contaminants. The interface between the EGaIn and the SAM thus includes a film of metal oxide, and probably also organic material adsorbed on this film; this interface will influence the properties and operation of the junctions. A combination of structural, chemical, and electrical characterizations leads to four conclusions about AgTS–S(CH2)n−1CH3//Ga2O3/EGaIn junctions. (i) The oxide is ∼0.7 nm thick on average, is composed mostly of Ga2O3, and appears to be self-limiting in its growth. (ii) The structure and composition (but not necessarily the contact area) of the junctions are conserved from junction to junction. (iii) The transport of charge through the junctions is dominated by the alkanethiolate SAM and not by the oxide or by the contaminants. (iv) The interface between the oxide and the eutectic alloy is rough at the micrometer scale., Chemistry and Chemical Biology

The liquid–metal eutectic of gallium and indium (EGaIn) is a useful electrode for making soft electrical contacts to self-assembled monolayers (SAMs). This electrode has, however, one feature whose effect on charge transport has been incompletely understood: a thin (approximately 0.7 nm) film—consisting primarily of Ga2O3—that covers its surface when in contact with air. SAMs that rectify current have been measured using this electrode in AgTS-SAM//Ga2O3/EGaIn (where AgTS = template-stripped Ag surface) junctions. This paper organizes evidence, both published and unpublished, showing that the molecular structure of the SAM (specifically, the presence of an accessible molecular orbital asymmetrically located within the SAM), not the difference between the electrodes or the characteristics of the Ga2O3 film, causes the observed rectification. By examining and ruling out potential mechanisms of rectification that rely either on the Ga2O3 film or on the asymmetry of the electrodes, this paper demonstrates that the structure of the SAM dominates charge transport through AgTS-SAM//Ga2O3/EGaIn junctions, and that the electrical characteristics of the Ga2O3 film have a negligible effect on these measurements., Chemistry and Chemical Biology

This paper compares the J(V) characteristics obtained for self-assembled monolayer (SAM)-based tunneling junctions with top electrodes of the liquid eutectic of gallium and indium (EGaIn) fabricated using two different procedures: (i) stabilizing the EGaIn electrode in PDMS microchannels and (ii) suspending the EGaIn electrode from the tip of a syringe. These two geometries of the EGaIn electrode (with, at least when in contact with air, its solid Ga2O3 surface film) produce indistinguishable data. The junctions incorporated SAMs of SCn–1CH3 (with n = 12, 14, 16, or 18) supported on ultraflat, template-stripped silver electrodes. Both methods generated high yields of junctions (70–85%) that were stable enough to conduct measurements of J(V) with statistically large numbers of data (N = 400–1000). The devices with the top electrode stabilized in microchannels also made it possible to conduct measurements of J(V) as a function of temperature, almost down to liquid nitrogen temperatures (T = 110–293 K). The J(V) characteristics were independent of T, and linear in the low-bias regime (−0.10 to 0.10V); the current density decreased exponentially with increasing thickness of the SAM. These observations indicate that tunneling is the main mechanism of charge transport across these junctions. Both methods gave values of the tunneling decay coefficient, β, of 1.0 nC–1 (0.80 Å–1), and the pre-exponential factor, J0 (which is a constant that includes contact resistance), of 3.0 × 102 A/cm2. Comparison of the electrical characteristics of the junctions generated using EGaIn by both methods against the results of other systems for measuring charge transport indicated that the value of β generated using EGaIn electrodes is compatible with the consensus of values reported in the literature. Although there is no consensus for the value of J0, the value of J0 estimated using the Ga2O3/EGaIn electrode is compatible with other values reported in the literature. The agreement of experimental values of β across a number of experimental platforms provides strong evidence that the structures of the SAMs—including their molecular and supramolecular structure, and their interfaces with the electrodes—dominate charge transport in both types of EGaIn junctions. These results establish that studies of J(V) characteristics of AgTS-SAM//Ga2O3/EGaIn junctions are dominated by the structure of the organic component of the SAM, and not by artifacts due to the electrodes, the resistance of the Ga2O3 surface film, or to the work functions of the metals., Chemistry and Chemical Biology

This paper applies statistical methods to analyze the large, noisy data sets produced in measurements of tunneling current density (J) through self-assembled monolayers (SAMs) in large-area junctions. It describes and compares the accuracy and precision of procedures for summarizing data for individual SAMs, for comparing two or more SAMs, and for determining the parameters of the Simmons model (β and J0). For data that contain significant numbers of outliers (i.e., most measurements of charge transport), commonly used statistical techniques—e.g., summarizing data with arithmetic mean and standard deviation and fitting data using a linear, least-squares algorithm—are prone to large errors. The paper recommends statistical methods that distinguish between real data and artifacts, subject to the assumption that real data (J) are independent and log-normally distributed. Selecting a precise and accurate (conditional on these assumptions) method yields updated values of β and J0 for charge transport across both odd and even n-alkanethiols (with 99% confidence intervals) and explains that the so-called odd–even effect (for n-alkanethiols on Ag) is largely due to a difference in J0 between odd and even n-alkanethiols. This conclusion is provisional, in that it depends to some extent on the statistical model assumed, and these assumptions must be tested by future experiments., Chemistry and Chemical Biology, Engineering and Applied Sciences

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. Methods and Findings: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. Conclusions: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy. Please see later in the article for the Editors' Summary

This paper describes the performance of junctions based on self-assembled monolayers (SAMs) as the functional element of a half-wave rectifier (a simple circuit that converts, or rectifies, an alternating current (AC) signal to a direct current (DC) signal). Junctions with SAMs of 11-(ferrocenyl)-1-undecanethiol or 11-(biferrocenyl)-1-undecanethiol on ultraflat, template-stripped Ag (AgTS) bottom electrodes, and contacted by top electrodes of eutectic indium–gallium (EGaIn), rectified AC signals, while similar junctions based on SAMs of 1-undecanethiol—SAMs lacking the ferrocenyl terminal group—did not. SAMs in these AC circuits (operating at 50 Hz) remain stable over a larger window of applied bias than in DC circuits. AC measurements, therefore, can investigate charge transport in SAM-based junctions at magnitudes of bias inaccessible to DC measurements. For junctions with SAMs of alkanethiols, combining the results from AC and DC measurements identifies two regimes of bias with different mechanisms of charge transport: (i) low bias (|V| < 1.3 V), at which direct tunneling dominates, and (ii) high bias (|V| > 1.3 V), at which Fowler–Nordheim (FN) tunneling dominates. For junctions with SAMs terminated by Fc moieties, the transition to FN tunneling occurs at |V| ≈ 2.0 V. Furthermore, at sufficient forward bias (V > 0.5 V), hopping makes a significant contribution to charge transport and occurs in series with direct tunneling (V 2.0 V) until FN tunneling activates (V 2.0 V). Thus, for Fc-terminated SAMs at forward bias, three regimes are apparent: (i) direct tunneling (V = 0–0.5 V), (ii) hopping plus direct tunneling (V ≈ 0.5–2.0 V), and (iii) FN tunneling (V 2.0 V). Since hopping does not occur at reverse bias, only two regimes are present over the measured range of reverse bias. This difference in the mechanisms of charge transport at forward and reverse bias for junctions with Fc moieties resulted in large rectification ratios (R > 100) and enabled half-wave rectification., Chemistry and Chemical Biology

This paper compares charge transport across self-assembled monolayers (SAMs) of n-alkanethiols containing odd and even numbers of methylenes. Ultraflat template-stripped silver (AgTS) surfaces support the SAMs, while top electrodes of eutectic gallium−indium (EGaIn) contact the SAMs to form metal/SAM//oxide/EGaIn junctions. The EGaIn spontaneously reacts with ambient oxygen to form a thin (1 nm) oxide layer. This oxide layer enables EGaIn to maintain a stable, conical shape (convenient for forming microcontacts to SAMs) while retaining the ability to deform and flow upon contacting a hard surface. Conical electrodes of EGaIn conform (at least partially) to SAMs and generate high yields of working junctions. Ga2O3/EGaIn top electrodes enable the collection of statistically significant numbers of data in convenient periods of time. The observed difference in charge transport between n-alkanethiols with odd and even numbers of methylenes — the “odd−even effect” — is statistically discernible using these junctions and demonstrates that this technique is sensitive to small differences in the structure and properties of the SAM. Alkanethiols with an even number of methylenes exhibit the expected exponential decrease in current density, J, with increasing chain length, as do alkanethiols with an odd number of methylenes. This trend disappears, however, when the two data sets are analyzed together: alkanethiols with an even number of methylenes typically show higher J than homologous alkanethiols with an odd number of methylenes. The precision of the present measurements and the statistical power of the present analysis are only sufficient to identify, with statistical confidence, the difference between an odd and even number of methylenes with respect to J, but not with respect to the tunneling decay constant, β, or the pre-exponential factor, J0. This paper includes a discussion of the possible origins of the odd−even effect but does not endorse a single explanation., Chemistry and Chemical Biology

Luminescent Os(II) and Ir(III) complexes containing a tripodal-type structure terminalized with three thiol derivatives are described. The tripod is introduced through derivatization, with a rigid spacer, of a phenanthroline ligand coordinated to the metal ion, and the entire structure possesses axial geometry. The geometry of the complexes combined with the three anchoring sites, the thiol groups, allows the complexes to adopt an almost perpendicular arrangement to the surfaces and the formation of a well-packed monolayer on Au substrates. The photophysical and electrochemical behavior of the complexes is studied in solution and on surfaces. Furthermore, a self-assembled monolayer (SAM) of Os(II) complexes on an ultraflat Au surface is used to fabricate a metal–molecule–metal junction with Au and In Ga eutectic as electrodes. The Os(II) SAM in the tunneling junction exhibits rectification behavior which is opposite in direction to that which we have previously shown for Ru(II) SAMs., Chemistry and Chemical Biology

Chemistry and Chemical Biology

This Account describes a strategy for fabricating multicomponent microsystems in which the structures of essentially all of the components are formed in a single step of micromolding. This strategy, which we call “cofabrication”, is an alternative to multilayer microfabrication, in which multiple layers of components are sequentially aligned (“registered”) and deposited on a substrate by photolithography. Cofabrication has several characteristics that make it an especially useful approach for building multicomponent microsystems. It rapidly and inexpensively generates correctly aligned components (for example, wires, heaters, magnetic field generators, optical waveguides, and microfluidic channels) over very large surface areas. By avoiding registration, the technique does not impose on substrates the size limitations of common registrations tools, such as steppers and contact aligners. We have demonstrated multicomponent microsystems with surface areas exceeding 100 \(cm^2\), but in principle, device size is only limited by the requirements of generating the original master. In addition, cofabrication can serve as a low-cost strategy for building microsystems. The technique is amenable to a variety of laboratory settings and uses fabrication tools that are less expensive than those used for multistep microfabrication. Moreover, the process requires only small amounts of solvent and photoresist, a costly chemical required for photolithography; in cofabrication, photoresist is applied and developed only once to produce a master, which is then used to produce multiple copies of molds containing the microfluidic channels. From a broad perspective, cofabrication represents a new processing paradigm in which the exterior (or shell) of the desired structures are produced before the interior (or core). This approach, generating the insulation or packaging structure first and injecting materials that provide function in channels in liquid phase, makes it possible to design and build microsystems with component materials that cannot be easily manipulated conventionally (such as solid materials with low melting points, liquid metals, liquid crystals, fused salts, foams, emulsions, gases, polymers, biomaterials, and fragile organics). Moreover, materials can be altered, removed, or replaced after the manufacturing stage. For example, cofabrication allows one to build devices in which a liquid flows through the device during use, or is replaced after use. Metal wires can be melted and reset by heating (in principle, repairing a break). This method leads to certain kinds of structures, such as integrated metallic wires with large cross-sectional areas or optical waveguides aligned in the same plane as microfluidic channels, that would be difficult or impossible to make with techniques such as sputter deposition or evaporation. This Account outlines the strategy of cofabrication and describes several applications. Specifically, we highlight cofabricated systems that combine microfluidics with (i) electrical wires for microheaters, electromagnets, and organic electrodes, (ii) fluidic optical components, such as optical waveguides, lenses, and light sources, (iii) gels for biological cell cultures, and (iv) droplets for compartmentalized chemical reactions, such as protein crystallization., Chemistry and Chemical Biology

This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, µPEDs). The µPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the µPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world., Chemistry and Chemical Biology

This paper describes a method of fabrication that generates small arrays of tunneling junctions based on self-assembled monolayers (SAMs); these junctions have liquid-metal top-electrodes stabilized in microchannels and ultraflat (template-stripped) bottom-electrodes. The yield of junctions generated using this method is high (70−90%). The junctions examined incorporated SAMs of alkanethiolates having ferrocene termini (11-(ferrocenyl)-1-undecanethiol, SC\(_{11}\)Fc); these junctions rectify currents with large rectification ratios (R), the majority of which fall within the range of 90−180. These values are larger than expected (theory predicts R ≤ 20) and are larger than previous experimental measurements. SAMs of n-alkanethiolates without the Fc groups (SC\(_{n−1}\)CH\(_3\), with n = 12, 14, 16, or 18) do not rectify (R ranged from 1.0 to 5.0). These arrays enable the measurement of the electrical characteristics of the junctions as a function of chemical structure, voltage, and temperature over the range of 110−293 K, with statistically large numbers of data (N = 300−800). The mechanism of rectification with Fc-terminated SAMs seems to be charge transport processes that change with the polarity of bias: from tunneling (at one bias) to hopping combined with tunneling (at the opposite bias)., Chemistry and Chemical Biology

This paper proposes a mechanism for the rectification of current by self-assembled monolayers (SAMs) of alkanethiolates with Fc head groups (SC\(_{11}\)Fc) in SAM-based tunneling junctions with ultra-flat Ag bottom electrodes and liquid metal (Ga\(_2\)O\(_3\)/EGaIn) top electrodes. A systematic physical-organic study based on statistically large numbers of data (N = 300−1000) reached the conclusion that only one energetically accessible molecular orbital (the HOMO of the Fc) is necessary to obtain large rectification ratios \(R \approx 1.0 \times 10^{2} (R = |J(−V)|/|J(V)|\) at \(±1\) V\()\). Values of R are log-normally distributed, with a log-standard deviation of 3.0. The HOMO level has to be positioned spatially asymmetrically inside the junctions (in these experiments, in contact with the Ga\(_2\)O\(_3\)/EGaIn top electrode, and separated from the Ag electrode by the SC\(_{11}\) moiety) and energetically below the Fermi levels of both electrodes to achieve rectification. The HOMO follows the potential of the Fermi level of the Ga\(_2\)O\(_3\)/EGaIn electrode; it overlaps energetically with both Fermi levels of the electrodes only in one direction of bias., Chemistry and Chemical Biology