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The development of wearable biosensors for continuous noninvasive monitoring of target biomarkers is limited to assays of a single sampled biofluid. An example of simultaneous noninvasive sampling and analysis of two different biofluids using a single wearable epidermal platform is demonstrated here. The concept is successfully realized through sweat stimulation (via transdermal pilocarpine delivery) at an anode, alongside extraction of interstitial fluid (ISF) at a cathode. The system thus allows on‐demand, controlled sampling of the two epidermal biofluids at the same time, at two physically separate locations (on the same flexible platform) containing different electrochemical biosensors for monitoring the corresponding biomarkers. Such a dual biofluid sampling and analysis concept is implemented using a cost‐effective screen‐printing technique with body‐compliant temporary tattoo materials and conformal wireless readout circuits to enable real‐time measurement of biomarkers in the sampled epidermal biofluids. The performance of the developed wearable device is demonstrated by measuring sweat‐alcohol and ISF‐glucose in human subjects consuming food and alcoholic drinks. The different compositions of sweat and ISF with good correlations of their chemical constituents to their blood levels make the developed platform extremely attractive for enhancing the power and scope of next‐generation noninvasive epidermal biosensing systems. A wearable dual iontophoresis tattoo for simultaneous detection of glucose in interstitial fluid‐ISF and alcohol in sweat is reported. A temporary tattoo electrode is used to perform reverse iontophoresis and pilocarpine iontophoretic delivery, simultaneously, to extract ISF‐glucose and sweat‐alcohol after eating and drinking. Variations in the glucose‐ISF and sweat‐alcohol concentrations correlate with the blood glucose and alcohol levels.

Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.Assessing progress towards designing reliable wearable biosensors reveals the challenges remaining before the promise of clinical translation can be realized.

The development of enzymatic biosensors and enzymatic biofuel cells (EBFCs) has been a significant area of research for decades. Enzymatic catalysis can provide for specific, reliable sensing of target analytes as well as the continuous generation of power from physiologically present fuels. However, the broad implementation of enzyme-based devices is still limited by low operational/storage stabilities and insufficient power densities. Approaches to improving upon these limitations have focused on the optimization of enzyme activity and electron transfer kinetics at enzyme-functionalized electrodes. Currently, such optimization can be performed through enzyme structural engineering, improvement of enzyme immobilization methodologies, and fabrication of advantageous electrode materials to enhance retained enzyme activity density at the electrode surface and electron transfer rates between enzymes and an electrode. In this work, varying electrode materials were studied to produce an increased understanding on the impacts of material properties on resulting biochemical, and electrochemical performances upon enzyme immobilization and an additional method of electroactive enzyme-based optimization was developed through the use of polymer-based protein engineering (PBPE). First, graphene/single-wall carbon nanotube cogels were studied as supports for membrane- and mediator-free EBFCs. The high available specific surface area and porosity of these materials allowed the rechargeable generation of a power density within one order of magnitude of the highest performing glucose-based EBFCs to date. Second, two additional carbon nanomaterial-based electrode materials were fabricated and examined as EBFC electrodes. Graphene-coated single-wall carbon nanotube gels and gold nanoparticle/multi-wall carbon nanotube-coated polyacrylonitrile fiber paddles were utilized as electroactive enzyme supports. The performance comparison of these three materials provided an increased understanding of the impact of material properties such as pore size, specific surface area and material surface curvature on enzyme biochemical and electrochemical characteristics upon immobilization. Third, PBPE techniques were applied to develop enzyme-redox polymer conjugates as a new platform for enzymatic biosensor and EBFC optimization. Poly(N-(3-dimethyl(ferrocenyl) methylammonium bromide)propyl acrylamide) (pFcAc) was grown directly from the surface of glucose oxidase (GOX) through atom-transfer radical polymerization. Utilization of the synthesized GOX-pFcAc conjugates led to a 24-fold increase in current generation efficiency and a 4-fold increase in EBFC power density compared to native GOX. GOX-pFcAc conjugates were further examined as working catalysts in carbon paper-based enzymatic biosensors, which provided reliable and selective glucose sensitivities and allowed a systematic analysis of sources of instability in enzyme-polymer conjugate-based biosensors and EBFCs. The knowledge gained through these studies and the in-depth characterization of an additional layer of optimization capacity using PBPE could potentially enhance the progress of enzymatic biosensor and EBFC development.

Gradually, through the BBC and later ITV, TV coverage built up despite a hostile, sustained campaign to resist it by the sport's then administrators. Fortuitously for Rupert Murdoch, whose media empire includes BSkyB, the barriers had been smashed by the time satellite television arrived at the end of the 1980s. Football was viewed by a man, whose business judgement is rarely wrong, as the opium of the masses and the quickest way to shift satellite dishes. By the time the ink was dry on the (pounds) 304m \"deal of the century\" contract for BSkyB to win the Premiership in 1992, football was hopelessly and helplessly betrothed to television. Anyone can be gripped by the thought of watching on BSkyB Manchester United versus Liverpool, but Oxford United playing Swindon Town on ITV Digital is altogether different. Since announcing the (pounds) 315m deal with the Football League, ITV Digital's subscriber base increased by just 238,000. In February, a nightly UK audience of 110,000 tuned into coverage of Nationwide football. That's 60,000 fewer than the 170,000 who read the Sunday Herald each week. Launched in 1998 as ONdigital and rebranded last year, ITV Digital - a joint venture between [Carlton] and Granada - was put into administration last week after swallowing (pounds) 800m of investment in its short lifetime. A (pounds) 315m deal with 72 English football clubs collapsed when the broadcaster was only able to offer (pounds) 50m.

Social distancing measures (e.g., avoiding travel, limiting physical contact with people outside of one's household, and maintaining a 1 or 2-metre distance between self and others when in public, depending on the country) are the primary strategies used to prevent transmission of the SARS-Cov-2 virus that causes COVID-19. Given that there is no effective treatment or vaccine for COVID-19, it is important to identify barriers and facilitators to adherence to social distancing to inform ongoing and future public health campaigns. This cross-sectional study was conducted online with a convenience sample of English-speaking adults. The survey was administered over the course of three weeks (March 30 -April 16, 2020) when social distancing measures were well-enforced in North America and Europe. Participants were asked to complete measures assessing socio-demographic characteristics, psychological constructs, including motivations to engage in social distancing, prosocial attitudes, distress, and social distancing behaviors. Descriptive (mean, standard deviation, percentage) and inferential statistics (logistic regression) were used to describes endorsement rates for various motivations, rates of adherence to social distancing recommendations, and predictors of adherence. Data were collected from 2013 adults living primarily in North America and Europe. Most frequently endorsed motivations to engage in social distancing (or facilitators) included \"I want to protect others\" (86%), \"I want to protect myself\" (84%), and I feel a sense of responsibility to protect our community\" (84%). Most frequently endorsed motivations against social distancing (or barriers) included \"There are many people walking on the streets in my area\" (31%), \"I have friends or family who need me to run errands for them\" (25%), \"I don't trust the messages my government provides about the pandemic\" (13%), and \"I feel stressed when I am alone or in isolation\" (13%). Adherence to social distancing recommendations ranged from 45% for \"working from home or remotely\" to 90% for \"avoiding crowded places/non-essential travel\", with men and younger individuals (18-24 years) showing lower adherence compared to women and older individuals. This study found that adherence to social distancing recommendations vary depending on the behaviour, with none of the surveyed behaviours showing perfect adherence. Strongest facilitators included wanting to protect the self, feeling a responsibility to protect the community, and being able to work/study remotely; strongest barriers included having friends or family who needed help with running errands and socializing in order to avoid feeling lonely. Future interventions to improve adherence to social distancing measures should couple individual-level strategies targeting key barriers to social distancing identified herein, with effective institutional measures and public health interventions. Public health campaigns should continue to highlight compassionate attitudes towards social distancing.

The outer blood retina barrier (oBRB) formed by the retinal pigment epithelium (RPE) is critical for maintaining retinal homeostasis. Critical to this modified neuro-epithelial barrier is the presence of the tight junction structure that is formed at the apical periphery of contacting cells. This tight junction complex mediates size-selective passive diffusion of solutes to and from the outer segments of the retina. Unlike other epithelial cells, the apical surface of the RPE is in direct contact with neural tissue and it is centrally involved in the daily phagocytosis of the effete tips of photoreceptor cells. While much is known about the intracellular trafficking of material within the RPE, less is known about the role of the tight junction complexes in health and diseased states. Here, we provide a succinct overview of the molecular composition of the RPE tight junction complex in addition to highlighting some of the most common retinopathies that involve a dysregulation of RPE integrity

G protein-coupled receptors (GPCRs) are the largest class of drug targets, largely owing to their druggability, diversity and physiological efficacy. Many drugs selectively target specific subtypes of GPCRs, but high specificity for individual GPCRs may not be desirable in complex multifactorial disease states in which multiple receptors may be involved. One approach is to target G protein subunits rather than the GPCRs directly. This approach has the potential to achieve broad efficacy by blocking pathways shared by multiple GPCRs. Additionally, because many GPCRs couple to multiple G protein signalling pathways, blocking specific G protein subunits can 'bias' GPCR signals by inhibiting only a subset of these signals. Molecules that target G protein α or βγ-subunits have been developed and show strong efficacy in multiple preclinical disease models and biased inhibition of G protein signalling. In this Review, we discuss the development and characterization of G protein α and βγ-subunit ligands and the preclinical evidence that this exciting new approach has potential for therapeutic efficacy in a number of indications, such as pain, thrombosis, asthma and heart failure.

Clinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow Minimal Residual Disease (MRD) negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool. Classification and risk-stratification for Acute Myeloid Leukemia (AML) at diagnosis are primarily based on cytogenetics and only a few gene mutations. Here, the authors study the genomic landscape of 3653 AML patients and characterize 16 non-overlapping molecular subgroups of clinical relevance for disease classification and risk prognostication.

Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P < 0.001) and smaller baseline diffusion lesion volume (Rho − 0.70, P < 0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P = 0.02) and relative (P < 0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho − 0.68, P < 0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P = 0.003) and relative (P = 0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.