Within-Person variations in mindfulness mediate effects of daily stressors on psychological distress in adolescence.

OBJECTIVE: We tested two competing models linking daily stress, mindfulness, and psychological distress in adolescence: 1) whether daily mindfulness moderates the impact of daily stressors on psychological distress or 2) whether mindfulness mediates the relationship between greater daily stressors and psychological distress. METHODS: Every evening for a week, 138 adolescents completed ecological momentary assessments (EMAs). Daily diaries assessed negative events, work-school conflict, mindfulness, and perceived stress. Multilevel mediation and moderation were tested. RESULTS: Results indicated that there were meaningful variations in adolescent mindfulness from day-to-day, and supported mediation rather than moderation; the within-person association between stressors and psychological distress was mediated by mindfulness at the daily level. CONCLUSION: It may be too challenging for adolescents to remain in a mindful state during stress to effectively use mindfulness as a buffer. Instead, daily stressors may indirectly impact psychological distress through decreasing mindfulness.

Optimal surveillance strategies for patients with stage 1 cutaneous melanoma post primary tumour excision: three systematic reviews and an economic model.

BACKGROUND: Malignant melanoma is the fifth most common cancer in the UK, with rates continuing to rise, resulting in considerable burden to patients and the NHS. OBJECTIVES: The objectives were to evaluate the effectiveness and cost-effectiveness of current and alternative follow-up strategies for stage IA and IB melanoma. REVIEW METHODS: Three systematic reviews were conducted. (1) The effectiveness of surveillance strategies. Outcomes were detection of new primaries, recurrences, metastases and survival. Risk of bias was assessed using the Cochrane Collaboration's Risk-of-Bias 2.0 tool. (2) Prediction models to stratify by risk of recurrence, metastases and survival. Model performance was assessed by study-reported measures of discrimination (e.g. D-statistic, Harrel's c-statistic), calibration (e.g. the Hosmer-Lemeshow 'goodness-of-fit' test) or overall performance (e.g. Brier score, R2). Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). (3) Diagnostic test accuracy of fine-needle biopsy and ultrasonography. Outcomes were detection of new primaries, recurrences, metastases and overall survival. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Review data and data from elsewhere were used to model the cost-effectiveness of alternative surveillance strategies and the value of further research. RESULTS: (1) The surveillance review included one randomised controlled trial. There was no evidence of a difference in new primary or recurrence detected (risk ratio 0.75, 95% confidence interval 0.43 to 1.31). Risk of bias was considered to be of some concern. Certainty of the evidence was low. (2) Eleven risk prediction models were identified. Discrimination measures were reported for six models, with the area under the operating curve ranging from 0.59 to 0.88. Three models reported calibration measures, with coefficients of ≥ 0.88. Overall performance was reported by two models. In one, the Brier score was slightly better than the American Joint Committee on Cancer scheme score. The other reported an R2 of 0.47 (95% confidence interval 0.45 to 0.49). All studies were judged to have a high risk of bias. (3) The diagnostic test accuracy review identified two studies. One study considered fine-needle biopsy and the other considered ultrasonography. The sensitivity and specificity for fine-needle biopsy were 0.94 (95% confidence interval 0.90 to 0.97) and 0.95 (95% confidence interval 0.90 to 0.97), respectively. For ultrasonography, sensitivity and specificity were 1.00 (95% confidence interval 0.03 to 1.00) and 0.99 (95% confidence interval 0.96 to 0.99), respectively. For the reference standards and flow and timing domains, the risk of bias was rated as being high for both studies. The cost-effectiveness results suggest that, over a lifetime, less intensive surveillance than recommended by the National Institute for Health and Care Excellence might be worthwhile. There was considerable uncertainty. Improving the diagnostic performance of cancer nurse specialists and introducing a risk prediction tool could be promising. Further research on transition probabilities between different stages of melanoma and on improving diagnostic accuracy would be of most value. LIMITATIONS: Overall, few data of limited quality were available, and these related to earlier versions of the American Joint Committee on Cancer staging. Consequently, there was considerable uncertainty in the economic evaluation. CONCLUSIONS: Despite adoption of rigorous methods, too few data are available to justify changes to the National Institute for Health and Care Excellence recommendations on surveillance. However, alternative strategies warrant further research, specifically on improving estimates of incidence, progression of recurrent disease; diagnostic accuracy and health-related quality of life; developing and evaluating risk stratification tools; and understanding patient preferences. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018086784. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol 25, No. 64. See the NIHR Journals Library website for further project information.

Malignant melanoma is the deadliest of skin cancers; in the UK, > 2500 people die from it every year. Initially, the cancer is removed surgically, which cures it for most people, but, for some, the cancer returns. For this reason, after a melanoma is removed, patients are followed up to see if the melanoma reoccurs or if new melanomas have developed. It is felt that early cancer detection improves the chance of future treatment working. A key question is how best to follow up patients after initial melanoma surgery. This study concentrates on the earliest stage of melanoma (American Joint Committee on Cancer stage I), which accounts for more than 7 out of 10 of all melanoma diagnoses. The study also investigates if new ways of follow-up could be at least as good as current practice and a better use of NHS money. We systematically reviewed studies comparing different ways of organising follow-up, and then methods to identify those patients at high risk of developing a further melanoma and how good different tests are at detecting this cancer. We then compared different possible follow-up strategies. For each strategy, we considered its impact on quality and length of life, and how well it used NHS resources. We found little evidence to support a change in how follow-up should be organised currently. There were some ways of organising follow-up that might be better than current care, but further research is needed. We found that new research on whether or not follow-up should be performed by a cancer nurse specialist, rather than a dermatologist or surgeon, would be worthwhile. We also found that more research could be worthwhile on how frequently melanoma recurs and spreads, as well as how accurately a diagnosis of further cancer is made and how to identify those most at risk of further melanoma spread.

Nanopore-Based Electrodes for Quinotrione Detection: Host-Guest-Induced Electrochemical Signal Switching.

Nanopore-based detection techniques, with a wide range of transport properties, exhibit impressive selectivity and sensitivity for analytes. To expand the application of nanoporous sensors, real-time and fast detection of targets, all within a portable device, is highly desired for nanopore-based sensors. In addition, to improve the accuracy of the output signal, more appropriate readout methods also need to be explored. In this manuscript, we describe a nanopore-based electrode, regarded as NAC-P6-PC@AuE, prepared by coupling a pillararene-based nanoporous membrane with an electrochemical impedance measurement method. The fabricated device is demonstrated by exposing pillararene-based receptors to trace amounts of pesticide molecules. NAC-P6-PC@AuE devices exhibit distinguished selectivity to quinotrione, as well as the ability to quantify quinotrione with a limit of quantitation (LOQ) of 10 nM. The mechanism that allows sensing was verified using finite-element simulations and may be explained as host-guest-induced surface charge shielding, which influences the electrochemical response of probe molecules. The applications of this nanopore-based electrode may be extended toward other target molecules by decorating the nanopore surfaces with specifically chosen receptors.

Tunable Nanopore Arrays as the Basis for Ionic Circuits.

There has been considerable interest in preparing ionic circuits capable of manipulating ionic and molecular transport in a solution. This direction of research is inspired by biological systems where multiple pores with different functionalities embedded in a cell membrane transmit external signals and underlie all physiological processes. In this manuscript, we describe the modeling of ion transport through small arrays of nanopores consisting of 3, 6, and 9 nanopores and an integrated gate electrode placed on the membrane surface next to one pore opening. We show that by tuning the gate voltage and strategically placing nanopores with nonlinear current-voltage characteristics, the local signal at the gate affects ionic transport through all nanopores in the array. Conditions were identified when the same gate voltage induced opposite rectification properties of neighboring nanopores. We also demonstrate that an ionic diode embedded in a nanopore array can modulate transport properties of neighboring pores even without a gate voltage. The results are explained by the role of concentration polarization and overlapping depletion zones on one side of the membrane. The modeling presented here is intended to become an inspiration to future experiments to create nanopore arrays that can transduce signals in space and time.

Ionic amplifying circuits inspired by electronics and biology.

Integrated circuits are present in all electronic devices, and enable signal amplification, modulation, and relay. Nature uses another type of circuits composed of channels in a cell membrane, which regulate and amplify transport of ions, not electrons and holes as is done in electronic systems. Here we show an abiotic ionic circuit that is inspired by concepts from electronics and biology. The circuit amplifies small ionic signals into ionic outputs, and its operation mimics the electronic Darlington amplifier composed of transistors. The individual transistors are pores equipped with three terminals including a gate that is able to enrich or deplete ions in the pore. The circuits we report function at gate voltages < 1 V, respond to sub-nA gate currents, and offer ion current amplification with a gain up to ~300. Ionic amplifiers are a logical step toward improving chemical and biochemical sensing, separations and amplification, among others.

An assessment of the limits of detection, sensitivity and specificity of three devices for public health-based drug checking of fentanyl in street-acquired samples.

BACKGROUND: Fentanyl has caused rapid increases in US and Canadian overdose deaths, yet its presence in illicit drugs is often unknown to consumers. This study examined the validity in identifying the presence of fentanyl of three portable devices that could be used in providing drug checking services and drug supply surveillance: fentanyl test strips, a hand-held Raman Spectrometer, and a desktop Fourier-Transform Infrared Spectrometer. METHODS: In Fall 2017, we first undertook an assessment of the limits of detection for fentanyl, then tested the three devices' sensitivity and specificity in distinguishing fentanyl in street-acquired drug samples. Utilizing test replicates of standard fentanyl reference material over a range of increasingly lower concentrations, we determined the lowest concentration reliably detected. To establish the sensitivity and specificity for fentanyl, 210 samples (106 fentanyl-positive, 104 fentanyl-negative) previously submitted by law enforcement entities to forensic laboratories in Baltimore, Maryland, and Providence, Rhode Island, were tested using the devices. All sample testing followed parallel and standardized protocols in the two labs. RESULTS: The lowest limit of detection (0.100 mcg/mL), false negative (3.7%), and false positive rate (9.6%) was found for fentanyl test strips, which also correctly detected two fentanyl analogs (acetyl fentanyl and furanyl fentanyl) alone or in the presence of another drug, in both powder and pill forms. While less sensitive and specific for fentanyl, the other devices conveyed additional relevant information including the percentage of fentanyl and presence of cutting agents and other drugs. CONCLUSION: Devices for fentanyl drug checking are available and valid. Drug checking services and drug supply surveillance should be considered and researched as part of public health responses to the opioid overdose crisis.

Employing the Payback Framework to Assess Implementation Science Research Utilization: Lessons From the USAID's PEPFAR HIV/AIDS Implementation Science Awards.

BACKGROUND: Stakeholders question whether implementation science (IS) is successful in conducting rigorous science that expedites the inclusion of health innovations into policies and accelerates the pace and scale of health service delivery into clinical and public health practice. Using the Payback Framework (PF) for research utilization (RU), we assessed the impact of USAID's IS investment on a subset of studies examining HIV prevention, care, and treatment. SETTING: Selected USAID-funded IS awards implemented between 2012 and 2017 in 9 sub-Saharan African countries. METHODS: A modified version of a RU framework, the PF, was applied to 10 USAID-funded IS awards. A semistructured, self-administered/interviewer-administered questionnaire representing operational items for the 5 categories of the modified PF was used to describe the type and to quantify the level of payback achieved. The raw score was tallied within and across the 5 PF categories, and the percentage of "payback" achieved by category was tabulated. Distribution of payback scores was summarized by tertiles. RESULTS: Knowledge production had the highest level of payback (75%), followed by benefits to future research (70%), benefits to policy (45%), benefits to health and the health system (18%), and broader economic benefits (5%). CONCLUSIONS: All awards achieved some level of knowledge production and benefits to future research, but translation to policy and programs was low and variable. We propose the use of policy, health system, and economic monitoring indicators of RU throughout the research process to increase IS studies' impact on health practice, programs, and policy.

Electrokinetic Phenomena in Organic Solvents.

Solid/liquid interfaces play a key role in separation processes, energy storage devices, and transport in nanoscale systems. Nanopores and mesopores with well-defined geometry and chemical characteristics have been a valuable tool to unravel electrochemical properties of interfaces, but the majority of studies have been focused on aqueous solutions. Here, we present experiments and numerical modeling aimed at characterizing effective surface charge of polymer pores in mixtures of water and alcohols as well as in propylene carbonate and acetone. The charge properties of pore walls are probed through analysis of current-voltage curves recorded in the presence of salt concentration gradients. The presence and direction of electro-osmotic flow lead to asymmetric current-voltage curves, with rectification characteristics determined by the polarity of surface charge. The results suggest that the effective surface charge of the pore walls depends not only on the type of solvent but also on the concentration of the electrolyte and voltage. We identified conditions at which polymer pores that are negatively charged in aqueous solutions become positively charged in propylene carbonate and acetone. The findings are of importance for nonaqueous separations, fundamental knowledge on solid/liquid interfaces in organic media, and preparation of porous devices with tunable surface charge characteristics.

Viscosity and Conductivity Tunable Diode-like Behavior for Meso- and Micropores.

Rectifying pores, which transport ions mainly in one direction blocking the ionic flow in the other, were shown to be important in the preparation of chemical sensors, components of ionic circuits, and mimics of biological channels. Ionic rectification has been shown with various engineered systems, but pores with similar opening diameters often rectify to a various uncontrolled extent. In this Letter we present a system of single meso-pores, whose current-voltage curves and rectification can be tuned with great precision via viscosity and conductivity gradients of solutions placed on both sides of the membrane. The mechanism of rectification is based on electroosmotically induced flow, which fills the entire volume of the pore with a single solution from either side of the membrane. The highly predictable rectifying system can find various applications, including measuring viscosity of unknown media and tuning electrokinetic passage of particles.

Influence of foot posture on the functioning of the windlass mechanism.

The absence of a functioning windlass mechanism may delay re-supination of the foot during locomotion and put excess stress on the mid-tarsal joint and soft tissues of the foot. The purpose of this study was to describe the foot posture of individuals that have an impaired or absent windlass mechanism. Forty-seven individuals (34 females and 13 males) with a mean age of 26 years were recruited to participate in this study. The Foot Posture Index was used to visually assess the posture of both feet. In addition, a digital gauge was used to measure dorsal arch height and midfoot width in bilateral resting standing. Dorsal arch height and mid-foot width were also measured in non-weight bearing. Finally, for those individuals without a functioning windlass mechanism, the amount of medial wedging needed to restore its function was measured. Subjects with an "absent" or "impaired" windlass mechanism had a mean Foot Posture Index of +6.8 (sd=2.5) compared to +2.5 (sd=3.1) for those with a functioning windlass mechanism. A series of independent t-tests showed that individuals without a functioning windlass mechanism had a more pronated foot posture, a lower dorsal arch height and a wider mid-foot width compared to those that had a functioning windlass mechanism. Finally, an average medial wedge of 5.1mm (sd=2.1) was able to produce a functioning windlass mechanism in those individuals that previously lacked one.