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Background This report describes how we refined a protocol for a pragmatic comparative effectiveness study of two models of an evidence-based diabetes shared medical appointment intervention and used the PRECIS-2 rating system to evaluate these adaptations. Methods We report primary data collected between June and August 2019, and protocol refinements completed between 2018 and 2020. Twenty-two members of the study team collaborated in protocol refinement and completed the PRECIS-2 ratings of study pragmatism. We discuss study design refinements made to achieve the desired level of pragmatism vs. experimental control for each of the nine PRECIS-2 dimensions. Study team members received training on PRECIS-2 scoring and were asked to rate the study protocol on the nine PRECIS-2 dimensions. Ratings were compared using descriptive statistics. Results In general, the PRECIS-2 ratings revealed high levels of pragmatism, but somewhat less pragmatic ratings on the categories of Delivery and Organization (costs and resources). This variation was purposeful, and we provide the rationale for and steps taken to obtain the targeted level of pragmatism on each PRECIS-2 dimension, as well as detail design changes made to a) make the design more pragmatic and b) address COVID-19 issues. There was general agreement among team members and across different types of stakeholders on PRECIS-2 ratings. Conclusions We discuss lessons learned from use of PRECIS-2 and experiences in refining the study to be maximally pragmatic on some dimensions and less so on other dimensions. This paper expands on prior research by describing actions to achieve higher levels of pragmatism and revise our protocol fit to the changed context. We make recommendations for future use of PRECIS-2 to help address changing context and other strategies for the planning of and transparent reporting on pragmatic research and comparative effectiveness research. Trial registration Clinicaltrials.gov Registration ID: NCT03590041.

Objective: Type 2 diabetes (T2D) affects 12% of U.S. adults and is a major public health burden. Shared medical appointments (SMAs) are an effective strategy to deliver diabetes self-management education and support (DSMES) alongside medical care, yet recruitment is a common challenge. Enhanced communication strategies have been recommended, while identifying specific messaging to engage patients with T2D remains needed. Methods: The Invested in Diabetes project is a cluster-randomized, pragmatic comparative effectiveness trial of two models of SMAs using an evidence-based DSMES curriculum. To aid recruitment at 22 primary care clinics, a group of patient, practice and research stakeholders used value proposition design strategies to develop tailored messaging on how SMAs can reduce pains and yield gains related to T2D. Patient stakeholders further refined messages to ensure patient-driven language. Here we describe value propositions for patients with newly diagnosed or uncontrolled T2D, diabetes distress, and comorbid conditions, plus concerned others. Results: General messaging emphasized how SMAs may help patients with T2D through expert education, addressing concerns, behavior change strategies, problem-solving, stress-coping skills, normalizing, and peer support. Messaging emphasized respect for autonomy (“you are your best health advocate”) coupled with available support (“you don’t have to go it alone”). For uncontrolled T2D, messages further conveyed opportunities to “finally take control” of T2D. For diabetes distress, messages also conveyed how SMAs may reduce feeling overwhelmed by T2D. Concerned others were encouraged to show support by telling patients about diabetes SMAs. Conclusions: Value proposition themes include how diabetes SMAs can improve T2D control and related stress, which may aid patient engagement. For clinics offering diabetes SMAs, messaging can be delivered by care team members and integrated into various recruitment activities. Disclosure N.D. Ritchie: None. A. Begum: None. J. Dailey-Vail: None. J. Rementer: None. R.A. Koren: None. S.A. Trujillo: None. P. Phimphasone-Brady: None. K.A. Cassidy: None. R. Wearner: None. J. Waxmonsky: None. B. Kwan: None. Funding Patient-Centered Outcomes Research Institute (IHS-1609-36322)

A field-effect transistor-based cortisol sensor was demonstrated in physiological conditions. An antibody-embedded polymer on the remote gate was proposed to overcome the Debye length issue (λ(D)). The sensing membrane was made by linking poly(styrene-co-methacrylic acid) (PSMA) with anticortisol before coating the modified polymer on the remote gate. The embedded receptor in the polymer showed sensitivity from 10 fg/mL to 10 ng/mL for cortisol and a limit of detection (LOD) of 1 pg/mL in 1× PBS where λ(D) is 0.2 nm. A LOD of 1 ng/mL was shown in lightly buffered artificial sweat. Finally, a sandwich ELISA confirmed the antibody binding activity of antibody-embedded PSMA.

Those involved in STEM outreach, from elementary schools through undergraduate students, all use varying teaching styles in an effort to instruct and inspire students. However, it is incredibly difficult to gauge or compare learning outcomes from new teaching techniques in situ. In this work, we describe the outcomes of a new undergraduate mini-course at Johns Hopkins University, Chocolate: An Introduction to Materials Science. In particular, the outcomes of teaching binary phase diagrams in this course using topical food examples were compared to the outcomes of the same instructor teaching a similar control group of students using standard textbook examples, reducing a number of confounding factors and allowing us to objectively analyze the benefits of using an atypical, popular approach to teach a standard subject. Results indicate that the students in the Chocolate course were not only more excited and engaged in the lecture, but they had identical or potentially greater learning gains than the control group.

NO2-responsive polymer-based organic field-effect transistors (OFETs) are described, and room-temperature detection with high sensitivity entirely from the semiconductor was achieved. Two thiophene polymers, poly(bisdodecylquaterthiophene) and poly(bisdodecylthioquaterthiophene) (PQT12 and PQTS12, respectively), were used as active layers to detect a concentration at least as low as 1 ppm of NO2. The proportional on-current change of OFETs using these polymers reached over 400% for PQTS12, which is among the highest sensitivities reported for a NO2-responsive device based on an organic semiconducting film. From measurements of cyclic voltammetry and the electronic characteristics, we found that the introduction of sulfurs into the side chains induces traps in films of the PQTS12 and also decreases domain sizes, both of which could contribute to the higher sensitivity of PQTS12 to NO2 gas compared with PQT12. The ratio of responses of PQTS12 and PQT12 is higher for exposures to lower concentrations, making...

Ammonia is a nearly ubiquitous environmental pollutant, and occupational or random exposure to sufficiently high levels is known to result in a variety of lung ailments. In this work, we present a flexible architecture for an ammonia inverter sensor consisting of a conductive plastic substrate, a bi-layer polymer dielectric, and patterned gold electrodes. n- and p-Type semiconductors (2,2′-[(2,5-dihexadecyl-3,6-dioxo-2,3,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1,4-diylidene)dithiene-5,2-diyli-dene]dimalononitrile (DPPCN) and poly(3-hexylthiophene-2,5-diyl) (P3HT), respectively) were deposited on the inverter in specific quantities in order to ensure complementary, reverse responses in the presence of ammonia gas. Our sensor shows a sensitivity down to 0.5 ppm ammonia, and has good stability in the presence of other vapors. The sturdy structure and easily understood transduction mechanism of this sensor make it potentially very useful for point-of-care sensing.

The strong and rational chemical interactions of molecular and polymeric organic semiconductors (OSCs) make the use of organic field-effect transistors (OFETs) compelling for vapor sensors. Gas-phase molecule detection is important for health monitoring and public security. This chapter highlights recent progress in OFET vapor sensors, emphasizing advances from the past 5 years and including aspects of OSC morphology and the role of adjacent dielectrics. In addition, means of designing the OSCs for increased sensitivity and selectivity are presented.

The strong and controllable chemical sensitivity of organic semiconductors (OSCs) and the amplification capability of transistors in circuits make use of OSC-based field-effect transistors compelling for chemical sensors. Analytes detected and assayed range from few-atom gas-phase molecules that may have adverse health and security implications to biomacromolecules (proteins, nucleic acids) that may be markers for physiological processes and medical conditions. This review highlights recent progress in organic field-effect transistor (OFET) chemical sensors, emphasizing advances from the past 5 years and including aspects of OSC morphology and the role of adjacent dielectrics. Design elements of the OSCs and various formats for the devices are illustrated and evaluated. Challenges associated with the present state of the art and future opportunities are also discussed.

We synthesized previously unreported copolymers with cleavable acid-labile side chains for use as electrochemical sensing layers in order to demonstrate a novel architecture for a one-step immunosensor. This one-step system is in contrast to most antigen-capture signal amplification methods that involve complicated secondary labeling techniques, or require the addition of redox probes to achieve a sensing response. A series of novel copolymers composed of various trityl-containing monomers were synthesized and characterized to determine their dielectric properties. The results indicate that the thin films of these polymers are stable in water, but some begin to degrade under acidic conditions or upon antigen binding, causing observable changes in the phase angle.

Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles that each subset plays in autoimmunity are not well studied. In this study, we show that circulating monocytes from patients with autoimmune uveitis exhibit a skewed phenotype toward intermediate CD14++CD16+ cells, and that this is associated with glucocorticoid therapy. We further demonstrate that CD14++CD16+ monocytes from patients and healthy control donors share a similar cell-surface marker and gene expression profile. Comparison of the effects of intermediate CD14++CD16+ monocytes with classical CD14++CD16− and nonclassical CD14+CD16++ monocytes revealed that the intermediate CD14++CD16+ subset had an attenuated capacity to promote both naive CD4+ T cell proliferation and polarization into a Th1 phenotype, and memory CD4+ T cell proliferation and IL-17 expression. Furthermore, CD14++CD16+ cells inhibit CD4+ T cell proliferation induced by other monocyte subsets and enhance CD4+ T regulatory cell IL-10 expression. These data demonstrate the impact of glucocorticoids on monocyte phenotype in the context of autoimmune disease and the differential effects of monocyte subsets on effector T cell responses.

A novel organic field effect transistor (OFET)-based biosensor is described for label-free glial fibrillary acidic protein detection. This study reports the first use of an extended solution gate structure where the sensing area and the organic semiconductor are separated, and a reference electrode is not needed. Different molecular weight polyethylene glycols (PEGs) are mixed into the bioreceptor layer to help extend the Debye screening length. The drain current change is significantly increased with the help of higher molecular weight PEGs, as they are known to reduce the dielectric constant. This study also investigates the sensing performance under different gate voltage (V g). The sensitivity increases after the V g is decreased from −5 to −2 V because the lower V g is much closer to the OFET threshold voltage and the influence of attached negatively charged proteins becomes more apparent. Finally, the selectivity experiments toward different interferents are performed. The stability and selectivity are promising for clinical applications.

Ethylene sensing is a highly challenging problem for the horticulture industry because of the limited physiochemical reactivity of ethylene. Ethylene plays a very important role in the fruit life cycle and has a significant role in determining the shelf life of fruits. Limited ethylene monitoring capability results in huge losses to the horticulture industry as fruits may spoil before they reach the consumer, or they may not ripen properly. Herein we present a poly(3-hexylthiophene-2,5-diyl) (P3HT)-based organic field effect transistor as a sensing platform for ethylene with sensitivity of 25 ppm V/V. To achieve this response, we used N-(tert-Butoxy-carbonyloxy)-phthalimide and palladium particles as additives to the P3HT film. N-(tert-Butoxy-carbonyloxy)-phthalimide is used to increase the porosity of the P3HT, thereby increasing the overall sensor surface area, whereas the palladium (1 μm diameter) particles are used as receptors for ethylene molecules in order to further enhance the sensitivity of the sensor platform. Both modifications give statistically significant sensitivity increases over pure P3HT. The sensor response is reversible and is also highly selective for ethylene compared to common solvent vapors.

We examined the potential of antibody-functionalized single-walled carbon nanotube (SWNT) field-effect transistors (FETs) for use as a fast and accurate sensor for a Lyme disease antigen. Biosensors were fabricated on oxidized silicon wafers using chemical vapor deposition grown carbon nanotubes that were functionalized using diazonium salts. Attachment of Borrelia burgdorferi (Lyme) flagellar antibodies to the nanotubes was verified by Atomic Force Microscopy and electronic measurements. A reproducible shift in the turn-off voltage of the semiconducting SWNT FETs was seen upon incubation with Borrelia burgdorferi flagellar antigen, indicative of the nanotube FET being locally gated by the residues of flagellar protein bound to the antibody. This sensor effectively detected antigen in buffer at concentrations as low as 1 ng/ml, and the response varied strongly over a concentration range coinciding with levels of clinical interest. Generalizable binding chemistry gives this biosensing platform the potential to be expanded to monitor other relevant antigens, enabling a multiple vector sensor for Lyme disease. The speed and sensitivity of this biosensor make it an ideal candidate for development as a medical diagnostic test., Comment: 10 pages, 3 figures, appears in Biosensors and Bioelectronics

Purpose AS101 is a non-toxic organotellurium-IV compound with demonstrated immunomodulating activity in vitro and in vivo. Inflammatory responses are attributed to the pathophysiology of numerous ocular diseases. In this study, we wished to elucidate whether AS101 could mitigate pro-inflammatory activity in human retinal pigment epithelial (RPE) cells, which are heavily involved in ocular immune responses, induced by pro-inflammatory IL-β activity. Methods Primary and transformed RPE cells treated with varying concentrations of AS101 were used in this study. Real-time PCR and ELISA assays were used to detect cytokine/chemokine mRNA expression and protein production. Western blot was used to detect changes in the NFκB pathway. Cell viability and proliferation were detected using a Vi-Cell XR cell counter. To measure the cytoprotective capacity of AS101, cell numbers were compared between cells treated with IL-1β or lipopolysaccharide (LPS) and cells treated with IL-1β or LPS in the presence of AS101. Results AS101 inhibited IL-1β-induced mRNA expression and protein production of IL-6 and IL-8 in RPE cells. The viability of RPE cells treated with IL-1β and LPS was unaffected. AS101 slightly inhibited RPE cell growth in the presence of higher levels of IL-1β. Also, AS101 downregulated the IL-1β activity by inhibiting the phosphorylation of p65, an NFκB subunit. Conclusions The results demonstrate that AS101 reduces IL-1β-induced inflammatory responses in the RPE. In previous studies, AS101 exhibited therapeutic effects in various disease models and was a safe profile in clinical trials. These results suggest that AS101 may have potent anti-inflammatory potential in the eye and confer the downregulation of RPE inflammatory responses in a pathological environment.

Electronic biosensing is a leading technology for determining concentrations of biomolecules. In some cases, the presence of an analyte molecule induces a measured change in current flow, while in other cases, a new potential difference is established. In the particular case of a field effect biosensor, the potential difference is monitored as a change in conductance elsewhere in the device, such as across a film of an underlying semiconductor. Often, the mechanisms that lead to these responses are not specifically determined. Because improved understanding of these mechanisms will lead to improved performance, it is important to highlight those studies where various mechanistic possibilities are investigated. This review explores a range of possible mechanistic contributions to field-effect biosensor signals. First, we define the field-effect biosensor and the chemical interactions that lead to the field effect, followed by a section on theoretical and mechanistic background. We then discuss materials used in field-effect biosensors and approaches to improving signals from field-effect biosensors. We specifically cover the biomolecule interactions that produce local electric fields, structures and processes at interfaces between bioanalyte solutions and electronic materials, semiconductors used in biochemical sensors, dielectric layers used in top-gated sensors, and mechanisms for converting the surface voltage change to higher signal/noise outputs in circuits.

We developed a novel detection method for osteopontin (OPN), a new biomarker for prostate cancer, by attaching a genetically engineered single chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube field-effect transistor (NTFET). Chemical functionalization using diazonium salts is used to covalently attach scFv to NT-FETs, as confirmed by atomic force microscopy, while preserving the activity of the biological binding site for OPN. Electron transport measurements indicate that functionalized NT-FET may be used to detect the binding of OPN to the complementary scFv protein. A concentration-dependent increase in the source-drain current is observed in the regime of clinical significance, with a detection limit of approximately 30 fM. The scFv-NT hybrid devices exhibit selectivity for OPN over other control proteins. These devices respond to the presence of OPN in a background of concentrated bovine serum albumin, without loss of signal. Based on these observations, the detection mechanism is attributed to changes in scattering at scFv protein-occupied defect sites on the carbon nanotube sidewall. The functionalization procedure described here is expected to be generalizable to any antibody containing an accessible amine group, and to result in biosensors appropriate for detection of corresponding complementary proteins at fM concentrations., Comment: 11 pages, 5 figures, appears in ACS Nano

Antibody-functionalized carbon nanotube devices have been suggested for use as bacterial detectors for monitoring of food purity in transit from the farm to the kitchen. Here we report progress towards that goal by demonstrating specific detection of Salmonella in complex nutrient broth solutions using nanotube transistors functionalized with covalently-bound anti-Salmonella antibodies. The small size of the active device region makes them compatible with integration in large-scale arrays. We find that the on-state current of the transistor is sensitive specifically to the Salmonella concentration and saturates at low concentration (, 8 pages, 3 figures, 1 table, appears in AIP Advances