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The rise of big data and smart sensing, with the promise of more educated and informed decisions, has fuelled a shift towards more data-driven decision-making in local and national government. However, we are observing a disconnect between the people who are affected by these decisions and their access to tools and resources to collect data in order to provide the needed evidence for change. To truly democratise this process and for citizens to become active prosumers of data, new mechanisms of citizen data production are needed. In this paper we report on a two-year ethnographic and iterative co-design process with the local community. This work encompassed the design, development and deployment of SenseMyStreet (SeMS), a bespoke sensor commissioning toolkit that enables citizens and community groups to use and commission a city's scientific-grade environmental monitors, determining where they will be located on their streets and collecting data to evidence hyper-local issues. Unlike prior research, which creates alternative data sources to contest city data, our toolkit helps integrate citizen commissioned data into the city datasets used by citizens and decision-makers. Reflecting on the design process and evaluating the ways people engaged with the digital tools of the toolkit, we highlight how commissioning can be configured to promote equity in the smart city, empower citizens to take ownership of issues and facilitate the creation of community networks that utilise the data for local benefit.

The transcription factor NF-κB is one of the central mediators of cellular signaling pathways. Under resting conditions, the canonical RelA-p50 (p65-p50) heterodimer NF-κB remains sequestered in the cytoplasm in complex with its inhibitor IκBα. Signal-mediated activation of NF-κB involves phosphorylation, ubiquitination and degradation of IκBα, and translocation of NF-κB to the nucleus. It was recently shown that a long non-coding RNA (termed NKILA) can modulate the NF-κB signaling circuit by interacting with the NF-κB-IκBα complex in the cytoplasm. In the current study, we investigated the interaction of RNA sequences derived from NKILA with domains of NF-κB and IκBα using NMR spectroscopy and native gel electrophoresis. Our results indicate that two RNA hairpin sequences interact with the DNA-binding domains of the Rel homology regions of RelA (p65) and p50, and that the same RNA sequences can affect the phosphorylation of the N-terminus of IκBα under low-salt conditions. We also observe that full-length RHR dimers (heterodimer of p65 and p50 and homodimer of p50) show a stronger interaction with the RNA hairpins than the individual domains of NF-κB. All of the interactions we observe between fragments of NKILA and domains of NF-κB are weak and non-specific, consistent with the proposed function of the NKILA-NF-κB-IκBα interaction in protecting the NFκB-IκBα complex from aberrant activation of the NF-κB signaling pathway.

This article presents six separate but connected understandings of a digital platform of listening vocabularies and protocols produced in the context of Listening Across Disciplines II, (LxDII) a cross- and transdisciplinary research project funded by the Arts and Humanities Research Council, UK (AHRC), conducted by the authors from 2018 to 2022. This research project set out to investigate and promote the use of listening across arts, humanities, science, and social science disciplines. To this end it worked with different partners from various fields to observe, co-work, and analyze, and finally to connect and compare different forms of listening. Early on it became clear that one of the main issues in establishing such a cross-disciplinary listening was the lack of a joint vocabulary and thus a means to share processes, methods, and insights. Therefore, it became a central objective to develop a resource of listening vocabularies and protocols that reveal differences as well as similarities and point to ways that connections can be established and methods shared. Subsequently, and to ensure cross-disciplinary and public use, these vocabularies and protocols were organized on an interactive digital platform, enabling browsing between methods and words, and hopefully affording shared approaches and cross-referencing. This article represents a reflection on the background, motivation, processes, and realization of this platform. It does so deliberately from the six listening positions of the research team. In this way it reproduces the project itself, in that it allows each listener their own understanding while connecting them through a shared platform. Please visit the online version of the journal to see and hear video and audio files.

This article examines debates, scholarly studies, and literary representations of the phenomenon of racism in socialist Yugoslavia and Yugoslavs’ relationship to whiteness in the 1960s and 70s. I argue that the persistent activism of black African students helped provoke official, scholarly, and public discussions about the thorny question of racism in Yugoslav society during this time. The salience of black students’ accusations eventually made something that was taboo in the 1950s and early 1960s—namely, entertaining the prospect that anti-black racial prejudice existed in non-aligned, socialist, and anti-racist Yugoslavia—into an active subject of debate by the end of the decade. Importantly, the relative candidness with which academic studies and popular literature addressed racism indicates a reflexivity about “racial” questions on the part of socialist Yugoslav society, something that scholarship has largely neglected in favor of focusing on the suppression or elision of race and the inadequacy of state socialist responses to the problem of domestic expressions of prejudice.

Purpose: to assess the likelihood of local recurrence of lung malignancies following stereotactic ablative radiotherapy (SABR) by evaluating clinical and radiomic features with machine learning and novel use of deep learning methods. Methods: pre-treatment CT images were attained from seventy patients with primary lung malignancies. The malignancy was segmented by the treating radiation oncologist and 107 radiomic features were extracted from the image. The data underwent feature reduction via Spearman’s correlation and selection with adapted LASSO regression analysis. A random forest model and a multilayer perceptron (MLP) with cost-sensitive classifier were independently used to assess for local recurrence of malignancy. The recurrence likelihood predictions from each of these were used to stratify patients into groups with high and low risk of recurrence. These were assessed for time-to-event predictions using Kaplan-Meier analyses and Gray’s test to evaluate the separation between the high and low-risk groups. The prognostic capacity of the models was evaluated with a concordance index, 95% confidence intervals and bootstrapping (10,000 iterations). Results: the MLP was able to predict the recurrence of malignancy with 100% sensitivity and 91% specificity (AUC 0.95). The MLP predictions showed statistically significant separation of high and low-risk patients, and robust model fit (p=0.04, c=0.79), which out-performed random forest model predictions (p=0.15, c=0.41) that did not reach statistical significance. Conclusions: radiomic data analysis with an MLP showed improved prediction potential within this dataset compared to random forest models for predicting local recurrence of lung cancer.

Healthcare services face difficulties in using structured methods for service design and having patient participation in such processes. There are few models on healthcare service design and even less focused on Primary Health Care (PHC) in the literature. Therefore, this paper contributes to this domain by presenting the proposal of a co-creative model to design PHC services. The proposed model was constructed based on the study of reference models in PHC and co-design. Plan-Do-Check-Act cycle and the Experience-Based Co-Design approach were used to structure the model. The resulting model contributes to (a) continuous improvement, (b) improvement analysis and registry, (c) identification and solution of PHC users' real needs, (d) community participation and empowerment, (e) creation of experience-focused and patient-centred services. The model's use of co-creation enables patients and PHC staff to understand each other's needs and challenges, and to create together appropriate solutions to their communities and act toward more satisfying services.

Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolated 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with an early ancestral strain of SARS-CoV-2 and later boosted with mRNA-1273. We characterized mAb genetic features by sequence assignments to the donors’ personal immunoglobulin genotypes and assessed antibody neutralizing activities against ancestral SARS-CoV-2, Beta, Delta, and Omicron variants. The mAbs used a broad range of immunoglobulin heavy chain (IGH) V genes in the response to all sub-determinants of the spike examined, with similar characteristics observed in both donors. IGH repertoire sequencing and B cell lineage tracing at longitudinal time points revealed extensive evolution of SARS-CoV-2 spike-binding antibodies from acute infection until vaccination five months later. These results demonstrate that highly polyclonal repertoires of affinity-matured memory B cells were efficiently recalled by vaccination, providing a basis for the potent antibody responses observed in convalescent persons following vaccination.

Porous ionic electrospray emitters have received significant interest for space propulsion due to their performance and operational simplicity. We have developed a diffusion equation for describing the transient flow response in a porous electrospray emitter, which allows for the prediction of the settling time for flow in the porous emitter. This equation accounts for both the change in liquid storage at exposed pores on the emitter with pressure, and viscous diffusion through Darcy's law. Transient flow solutions are provided for the most common emitter topologies: pillar, cone, and wedge. Transient flow solutions describe the settling time and magnitude of current overshoot from porous electrosprays. Comparing diffusion of pressure to the onset delay model for electrospray emission shows that diffusion is most relevant at higher voltages and when a porous reservoir is used. Accounting for multiple emission sites on the wedge geometry shows that emission sites settle in proportion to emission site spacing to the power -1.74. Applying the diffusion equation to published results shows good agreement between analytical predictions and experimental data.

This article considers Participatory Arts and sociocultural understandings of justice and praxis through the example of Big hART, an Australian multi-award winning provider where both artists and participants – often disenfranchised and marginalised young people – co-create the work (Matarasso, 2018). Enacting social justice principles, Big hART works alongside young people to improve their life outcomes through arts practice strengthening young people’s critical capabilities by inducting them as both makers and responders to their own lives and the world around them. Drawing on three years of ethnographic research across three sites in rural and regional Australia we highlight how multidimensional and multi-modal arts-based projects contribute to young people’s lives through theorising the attributes and dimensions of twenty productive conditions and practices identified as essential for social change. These possibilities are important as when these conditions are purposefully enacted, the power of the arts for sense-making and identity development is revealed in non-formal learning spaces. Theoretically unpacking these conditions and practices and linking them with research outcomes helps build understanding of the generative power of Participatory Arts through the ways Big hART builds bridges between young people and their communities and the developmental trajectories they may take through being ‘at-promise’ rather than ‘at-risk’.

BACKGROUND: Transcriptional remodeling is known to contribute to heart failure (HF). Targeting stress-dependent gene expression mechanisms may represent a clinically relevant gene therapy option. We recently uncovered a salutary mechanism in the heart whereby junctophilin-2 (JP2), an essential component of the E-C coupling apparatus, is site-specifically cleaved and releases an N-terminal fragment (JP2NT) that translocates into the nucleus and functions as a transcriptional repressor of HF-related genes. This study aims to determine whether JP2NT can be leveraged by gene therapy techniques for attenuating HF progression in a pre-clinical pressure overload model. METHODS: We intraventricularly injected AAV(2/9) vectors expressing eGFP, JP2NT, or DNA-binding deficient JP2NT (JP2NT(ΔbNLS/ARR)) into neonatal mice and induced cardiac stress by trans-aortic constriction (TAC) 9 weeks later. We also treated mice with established moderate HF from TAC stress with either AAV-JP2NT or AAV-eGFP. RNA-Seq analysis was used to reveal changes in hypertrophic and HF-related gene transcription by JP2NT gene therapy after TAC. Echocardiography, confocal imaging and histology were performed to evaluate heart function and pathological myocardial remodeling following stress. RESULTS: Mice pre-injected with AAV-JP2NT exhibited ameliorated cardiac remodeling following TAC. The JP2NT DNA binding domain is required for cardioprotection as its deletion within the AAV-JP2NT vector prevented improvement in TAC-induced cardiac dysfunction. Functional and histological data suggest that JP2NT gene therapy after the onset of cardiac dysfunction is effective at slowing the progression of HF. RNA-Seq analysis further revealed a broad reversal of hypertrophic and HF-related gene transcription by JP2NT overexpression after TAC. CONCLUSIONS: Our prevention- and intervention- based approaches here demonstrated that AAV-mediated delivery of JP2NT into the myocardium can attenuate stress-induced transcriptional remodeling and the development of HF when administered either before or after cardiac stress initiation. Our data indicate that JP2NT gene therapy holds great potential as a novel therapeutic for treating hypertrophy and HF.

IntroductionAlopecia areata (AA) is an autoimmune disease characterized by hair loss. Patients with AA experience a range of social and emotional impacts, and the lack of effective treatments and multiple affected locations can deepen the burden of illness. The objective of the current study was to assess health-related quality of life (HRQL) among patients with AA, and to evaluate the relationship between patient-reported AA severity, HRQL and treatment patterns.MethodsA web survey was completed by participants recruited through the National Alopecia Areata Foundation. The survey included questions on disease characteristics, burden and impact (evaluated by the Skindex-16 for AA and items on work/school and sexual relationships), healthcare utilization and treatment experience. Analyses were conducted for the overall sample and by key subgroups, including AA severity and disease duration.ResultsA total of 1327 participants with AA completed the survey. The mean age was 39.7 [standard deviation (SD) 12.3]years and 58.4% were female. On average, participants had experienced signs and symptoms of AA for 11.5 years(SD 12.5) and were diagnosed by a healthcare provider (HCP) 10.5(SD 12.2) years ago. Participants reported a range of severity of current scalp hair loss, including 0% (2.6%), 1-20% (39.8%), 21-49% (26.2%), 50-94% (10.2%) and 95-100% (21.3%). Participants reporting 95-100% of scalp hair missing were less likely to be currently seeing an HCP and to currently be on treatments for AA. There was a non-linear relationship between HRQL and current AA severity. Participants with 1-20% to 50-94% of current scalp hair missing reported higher symptom, functioning and emotional impacts due to AA than participants with 0% missing scalp hair and/or 95-100% missing scalp hair. Similar findings were observed for current eyebrow and eyelash severity, except for emotional impacts.ConclusionSeverity of AA plays an important role in understanding the burden of illness and healthcare patterns of people living with AA.

White spruce (Picea glauca) emits monoterpenes that function as defensive signals and weapons after herbivore attack. We assessed the effects of drought and methyl jasmonate (MeJA) treatment, used as a proxy for herbivory, on monoterpenes and other isoprenoids in P. glauca. The emission of monoterpenes was significantly increased after MeJA treatment compared to the control, but drought suppressed the MeJA-induced increase. The composition of the emitted blend was altered strongly by stress, with drought increasing the proportion of oxygenated compounds and MeJA increasing the proportion of induced compounds such as linalool and (E)-β-ocimene. In contrast, no treatment had any significant effect on the levels of stored monoterpenes and diterpenes. Among other MEP pathway-derived isoprenoids, MeJA treatment decreased chlorophyll levels by 40%, but had no effect on carotenoids, while drought stress had no impact on either of these pigment classes. Of the three described spruce genes encoding 1-deoxy-D-xylulose-5-phosphate synthase (DXS) catalyzing the first step of the MEP pathway, the expression of only one, DXS2B, was affected by our treatments, being increased by MeJA and decreased by drought. These findings show the sensitivity of monoterpene emission to biotic and abiotic stress regimes, and the mediation of the response by DXS genes.

Experience Based Co-Design (EBCD) has become a popular way of using experience for healthcare service improvement. Despite its popularity, there are few comparative studies on the use of the approa...

Study purpose Out-of-hospital cardiac arrests (OHCA) in the young population have only been examined in a limited number of regional studies. Hence, we sought to describe OHCA characteristics and predictors of survival to hospital discharge for the young Irish population. Study design An observational analysis of the national Irish OHCA register for all OHCAs aged ≤35 years between January 2012 and December 2017 was performed. The young population was categorised into three age groups: ≤1 year, 1–15 years and 16–35 years. Multivariable logistic regression was used to determine the independent predictors of survival to hospital discharge. Results A total of 1295 OHCAs aged ≤35 years (26.9% female, median age 25 (IQR 17–31)) had resuscitation attempted. OHCAs in those aged ≥16 years (n=1005) were more likely to happen outside the home (38.5% vs 22.8%, p Conclusions The high prevalence of non-medical OHCAs and the OHCA location need to be considered when developing OHCA care pathways and preventative strategies to reduce the burden of OHCAs in the young population.

This mixed media contribution investigates the multiple modes of inscription possible within a practice-based investigation of the Sonic Anthropocene. Drawing upon critical contexts from Geology, Geography and Anthropology, and the relations between writing, bodies and earthly matters, the authors suggest a re-writing occurs in mediated acts such as field recording (phonography). Microphonic translations from the field not only re-inscribe sites, plural; they reveal sound’s itinerant nature to be full of duplicitous and fictive potential. Operating such possibility through the practice of Foley, the post production art of material based sound effects, the authors pivot discussions around their soundwork Decoys (2018) and its attempt to address the urgency of anthropogenic change through a latticing of source and signal, site and studio, subject and observer, human and more-than-human.

Background The epidemiology and outcome after out-of-hospital cardiac arrest (OHCA) varies across Europe. Following on from EuReCa ONE, the aim of this study was to further explore the incidence of and outcomes from OHCA in Europe and to improve understanding of the role of the bystander. Methods This prospective, multicentre study involved the collection of registry-based data over a three-month period (1st October 2017 to 31st December 2017). The core study dataset complied with the Utstein-style. Primary outcomes were return of spontaneous circulation (ROSC) and survival to hospital admission. Secondary outcome was survival to hospital discharge. Results All 28 countries provided data, covering a total population of 178,879,118. A total of 37,054 OHCA were confirmed, with CPR being started in 25,171 cases. The bystander cardiopulmonary resuscitation (CPR) rate ranged from 13% to 82% between countries (average: 58%). In one third of cases (33%) ROSC was achieved and 8% of patients were discharged from hospital alive. Survival to hospital discharge was higher in patients when a bystander performed CPR with ventilations, compared to compression-only CPR (14% vs. 8% respectively). Conclusion In addition to increasing our understanding of the role of bystander CPR within Europe, EuReCa TWO has confirmed large variation in OHCA incidence, characteristics and outcome, and highlighted the extent to which OHCA is a public health burden across Europe. Unexplained variation remains and the EuReCa network has a continuing role to play in improving the quality management of resuscitation. info:eu-repo/semantics/publishedVersion

Significance Intrinsically disordered proteins must frequently compete for binding to shared interaction hubs to perform their cellular functions. Here, we describe the mechanism by which two disordered proteins that regulate the transcriptional response to hypoxia compete for binding to the folded TAZ1 domain of the transcriptional coactivators CBP and p300. CITED2, a negative feedback regulator of HIF-1α, displaces HIF-1α from TAZ1 in a unidirectional, switch-like manner. Efficient competition for binding of the TAZ1 domain is highly dependent on the flexibility and multivalency of the HIF-1α and CITED2 activation domains. Differences in the strength of coupling of the CITED2 and HIF-1α binding motifs are key determinants of unidirectionality and underscore the role of multivalency in regulation of cellular processes by disordered proteins., Intrinsically disordered proteins must compete for binding to common regulatory targets to carry out their biological functions. Previously, we showed that the activation domains of two disordered proteins, the transcription factor HIF-1α and its negative regulator CITED2, function as a unidirectional, allosteric molecular switch to control transcription of critical adaptive genes under conditions of oxygen deprivation. These proteins achieve transcriptional control by competing for binding to the TAZ1 domain of the transcriptional coactivators CREB-binding protein (CBP) and p300 (CREB: cyclic-AMP response element binding protein). To characterize the mechanistic details behind this molecular switch, we used solution NMR spectroscopy and complementary biophysical methods to determine the contributions of individual binding motifs in CITED2 to the overall competition process. An N-terminal region of the CITED2 activation domain, which forms a helix when bound to TAZ1, plays a critical role in initiating competition with HIF-1α by enabling formation of a ternary complex in a process that is highly dependent on the dynamics and disorder of the competing partners. Two other conserved binding motifs in CITED2, the LPEL motif and an aromatic/hydrophobic motif that we term ϕC, function synergistically to enhance binding of CITED2 and inhibit rebinding of HIF-1α. The apparent unidirectionality of competition between HIF-1α and CITED2 is lost when one or more of these binding regions is altered by truncation or mutation of the CITED2 peptide. Our findings illustrate the complexity of molecular interactions involving disordered proteins containing multivalent interaction motifs and provide insight into the unique mechanisms by which disordered proteins compete for occupancy of common molecular targets within the cell.

Listening After Nature questions the reality of auditory natures. It argues that the line between wilderness and industrial culture is dull, and the natural world is presently a critical construct that entangles humans, animals, sites and technologies. Bringing new insights to the field of environmental sound arts in areas such as field recording, acoustic ecology and soundscape studies, Wright examines contemporary and archival audio works and calls for a ‘post-natural’ approach to sound. The book propels sounds arts discourse into critical relationship with the environmental humanities and contemporary approaches dealing with the consequences of Anthropogenic change. Critical and imaginative, this is a book that forges urgent debate between sound, ethics, aesthetics and ecology.

Background Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline available on the methods to assess physical performance and function in this population. The purpose was to systematically compile and describe assessments of physical performance and function in patients and survivors of pediatric cancer, including cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait and motor performance test batteries. Methods We searched the databases PubMed, SPORTDiscus, and Cochrane Database and performed abstract and full-text selection of 2619 articles according to the Cochrane Handbook of Systematic Reviews. Information on patients characteristics, assessments, information on validity and reliability, and relevant references was extracted. Results In summary, 63 different assessments were found in 149 studies including 11639 participants. Most studies evaluated cardiorespiratory fitness and muscle strength with the majority conducted off treatment. Some outcomes (e.g. speed) and diagnoses (e.g. neuroblastoma) were severely underrepresented. With the exception of gait, leukemia patients represented the largest group of individuals tested. Conclusions Insufficient data and patient heterogeneity complicate uniform recommendations for assessments. Our results support researchers and practitioners in selecting appropriate assessment to meet their specific research questions or individual daily practice needs. Impact This systematic review includes 149 studies and provides a comprehensive summary of 63 assessments to evaluate cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait or motor performance test batteries in patients and survivors of pediatric cancer. We present the most studied fields within the pediatric cancer population, which are cardiorespiratory fitness and muscle strength, off treatment phase, and leukemia patients. We propose research priorities by identification of subgroups in terms of cancer type, phase of treatment, and outcome of interest that are underrepresented in studies currently available.

Objective: To investigate the effect of a new therapeutic approach, using an oscillating rod to strength the pelvic floor and deep abdominal musculature and to speed up recovery of continence after radical prostatectomy. Design: Prospective randomized controlled clinical trial. Setting: Inpatient uro-oncology rehabilitation clinic. Subjects: Ninety-three (intervention group (IG)) and ninety-one patients (control group (CG)) with urinary incontinence after prostatectomy were examined. Intervention: All patients were randomly allocated to either standard pelvic floor muscle exercises and oscillating rod therapy (IG) or standard pelvic floor muscle exercises and relaxation therapy (CG). Main outcome measures: Urinary incontinence (1- and 24-hour pad test) was assessed, and health-related quality of life (HRQL; Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire) was measured for all patients before and after three weeks of treatment. Results: One hundred and eighty-four patients (mean (SD) age: 64.1 (6.94) years) completed the study. The IG showed a significant reduction in urinary incontinence (1-hour pad test: P = 0.008, 24-hour pad test: P = 0.012) and a significant improvement of HRQL ( P = 0.017) compared with CG. Continence was significantly improved in both groups (1-hour pad test: 22.6–8.5 g (IG) vs. 23.0–18.1 g (CG)/24-hour pad test: 242.9–126.7 g (IG) vs. 237.6–180.9 g (CG)). Conclusion: The study demonstrated that a combination of conventional continence exercises and the new oscillation rod training increased abdominal and pelvic floor musculature and speeded up recovery of continence after radical prostatectomy.

A response to the Quanta article about a Twitter spat triggered by comments in the Guardian by Sabine Hossenfelder.

This study aimed to assess (i) COVID‐19 transmission prior to and following spectator events and (ii) methodological approaches to capturing event‐related transmission during the spectator return. Local authority population transmission rates were used to identify higher transmission areas, which were excluded from participant attendance following registration. Using observational online and SMS questionnaires, self‐reported COVID‐19 diagnoses (positive tests) and racing‐related NHS Test and Trace contacts within 14 days of spectating were reported for two British Horseracing events and three Point to Point (PTP) grassroots races. There were 1,477 registrations for the British Horseracing events, and 1,678 registrations for PTP races. Responses were received from 464 attendees of British Horseracing events (31.4% response rate). Two attendees reported a COVID‐19 diagnosis, and no attendees reported NHS Test and Trace contact. From PTP races, 862 attendees (51.3%) consented to receive the SMS survey, and responses were received from 495 attendees (57.4% response rate). Five attendees reported positive COVID‐19 diagnoses, and two attendees reported being contacted by NHS Test and Trace, of which one was following a non‐racing potential COVID‐19 exposure. There was limited evidence of COVID‐19 transmission at outdoor elite and grassroots level horseracing events during autumn 2020. A higher response rate was received with SMS surveys; however, there was a reluctancy to “opt in” to SMS methodology. This study describes different methodological approaches to monitoring COVID‐19 transmission risk at events, which may have relevance for other sporting and event contexts during the current pandemic, and sustained attendances during periods with circulating transmissible diseases.

Beta-adrenoceptors (βAR) are often viewed as archetypal G-protein coupled receptors. Over the past fifteen years, investigations in cardiovascular biology have provided remarkable insights into this receptor family. These studies have shifted pharmacological dogma, from one which centralized the receptor to a new focus on structural micro-domains such as caveolae and t-tubules. Important studies have examined, separately, the structural compartmentation of ion channels and βAR. Despite links being assumed, relatively few studies have specifically examined the direct link between structural remodeling and electrical remodeling with a focus on βAR. In this review, we will examine the nature of receptor and ion channel dysfunction on a substrate of cardiomyocyte microdomain remodeling, as well as the likely ramifications for cardiac electrophysiology. We will then discuss the advances in methodologies in this area with a specific focus on super-resolution microscopy, fluorescent imaging, and new approaches involving microdomain specific, polymer-based agonists. The advent of powerful computational modelling approaches has allowed the science to shift from purely empirical work, and may allow future investigations based on prediction. Issues such as the cross-reactivity of receptors and cellular heterogeneity will also be discussed. Finally, we will speculate as to the potential developments within this field over the next ten years.

Background Survival after out-of-hospital cardiac arrest (OHCA) is still low. For every minute without resuscitation the likelihood of survival decreases. One critical step is initiation of immediate, high quality cardiopulmonary resuscitation (CPR). The aim of this subgroup analysis of data collected for the European Registry of Cardiac Arrest Study number 2 (EuReCa TWO) was to investigate the association between OHCA survival and two types of bystander CPR namely: chest compression only CPR (CConly) and CPR with chest compressions and ventilations (FullCPR). Method In this subgroup analysis of EuReCa TWO, all patients who received bystander CPR were included. Outcomes were return of spontaneous circulation and survival to 30-days or hospital discharge. A multilevel binary logistic regression analysis with survival as the dependent variable was performed. Results A total of 5884 patients were included in the analysis, varying between countries from 21 to 1444. Survival was 320 (8%) in the CConly group and 174 (13%) in the FullCPR group. After adjustment for age, sex, location, rhythm, cause, time to scene, witnessed collapse and country, patients who received FullCPR had a significantly higher survival rate when compared to those who received CConly (adjusted odds ration 1.46, 95% confidence interval 1.17–1.83). Conclusion In this analysis, FullCPR was associated with higher survival compared to CConly. Guidelines should continue to emphasise the importance of compressions and ventilations during resuscitation for patients who suffer OHCA and CPR courses should continue to teach both.