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β-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor-β-arrestin interactions at the plasma membrane of living cells remain elusive. Here, we combine single-molecule microscopy with molecular dynamics simulations to dissect the complex sequence of events involved in β-arrestin interactions with both receptors and the lipid bilayer. Unexpectedly, our results reveal that β-arrestin spontaneously inserts into the lipid bilayer and transiently interacts with receptors via lateral diffusion on the plasma membrane. Moreover, they indicate that, following receptor interaction, the plasma membrane stabilizes β-arrestin in a longer-lived, membrane-bound state, allowing it to diffuse to clathrin-coated pits separately from the activating receptor. These results expand our current understanding of β-arrestin function at the plasma membrane, revealing a critical role for β-arrestin preassociation with the lipid bilayer in facilitating its interactions with receptors and subsequent activation.

Graphical abstract, Highlights • BCI encompasses a spectrum of cardiac injuries. • BCI should be considered in all patients with major thoracoabdominal trauma. • TEE is an excellent imaging method for evaluating BCI, including atrioventricular valve injury.

We conducted a survey of Australian and New Zealand anaesthetists designed to quantify self-reported use of cricoid pressure (CP) in patients presumed to be at risk of gastric regurgitation, and to ascertain the underlying justifications used to support individual practice. We aimed to identify the perceived benefits and harms associated with the use of CP and to explore the potential impact of medicolegal concerns on clinical decision-making. We also sought to ascertain the views of Australian and New Zealand anaesthetists on whether recommendations relating to CP should be included in airway management guidelines. We designed an electronic survey comprised of 15 questions that was emailed to 981 randomly selected Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) by the ANZCA Clinical Trials Network on behalf of the investigators. We received responses from 348 invitees (response rate 35.5%). Of the 348 respondents, 267 (76.9%) indicated that they would routinely use CP for patients determined to be at increased risk of gastric regurgitation. When asked whether participants believed the use of CP reduces the risk of gastric regurgitation, 39.8% indicated yes, 23.8% believed no and 36.3% were unsure. Of the respondents who indicated that they routinely performed CP, 159/267 (60%) indicated that concerns over the potential medicolegal consequences of omitting CP in a patient who subsequently aspirates was one of the main reasons for using CP. The majority (224/337; 66%) of respondents believed that recommendations about the use of CP in airway management guidelines should include individual practitioner judgement, while only 55/337 (16%) respondents believed that routine CP should be advocated in contemporary emergency airway management guidelines.

Motivated in part by the bi-gravity approach to massive gravity, we introduce and study the multimetric Finsler geometry. For the case of an arbitrary number of dimensions, we study some general properties of the geometry in terms of its Riemannian ingredients, while in the 2-dimensional case, we derive all the Cartan equations as well as explicitly find the Holmes-Thompson measure., Comment: 27 pages

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

This chapter discusses the management of the emergency patient. It begins with tracheal intubation of critically ill adults then discusses sepsis and septic shock, the emergency laparotomy, the ICU patient going to theatre and transferring the critically ill.

Aims Attending the paediatric emergency department (PED) and acute assessment units can be a daunting and stressful experience for patients and carers. We aimed to evaluate their experience of PED and acute assessment unit visits. Methods Data was captured using the validated RCPCH Patient Reported Experience Measure (PREM) for urgent and emergency care. This questionnaire was initially given out in 2013 and again in 2019 and included the views of patients, if over 8 years old, and/or carers. Completion of forms was voluntary and anonymised. In 2019 all respondents were offered the opportunity to take part in semi-structured interviews to explore their experiences in detail. Interviewees completed a questionnaire prior to the interview where they ranked the elements they most valued with regards to urgent care visits. This was used to scaffold the interview. Data was collected by 2 researchers, who transcribed verbatim, and by participants’ written reports. In 2019 data was collected over a three-week period. All data collection and analyses were carried out by individuals independent from the clinical team. Qualitative data was thematically analysed by four researchers. This was the second part of an audit cycle. Results In 2019 51 (18 involving patients) responses to the PREM questionnaire were collected and 12 interviews (4 involving patients) took place (20–30 minutes long). The majority described ED experience positively. From the PREM questionnaire key strengths included addressing pain in a timely manner and safety netting. Areas that need improvement include updates when waiting and advice on when to resume normal activities. From the interviews, communication and safety were identified as priorities. The provision of detailed information in a timely manner was highly valued, alongside feeling listened to by staff. Safety had three dimensions: physical, clinical and psychological/emotional. Waiting times and environmental factors also were valued but were less than other factors above. Conclusions Communication is highly valued, but improvements are required to provide contemporaneous information. This is congruent with existing literature highlighting parent disempowerment in acute care settings and underlining the importance of timely updates. Good communication improved carers’ feelings of psychological and emotional safety.

We study the spectral action approach to higher derivative gravity. The work focuses on the classical aspects. We derive the complete and simplified form of the purely gravitational action up to the 6-derivative terms. We also derive the equivalent forms of the action, which might prove useful in different applications, namely Riemann- and Weyl-dominated representations. The spectral action provides a rather rigid structure of the higher derivative part of the theory. We discuss the possible consequences of this rigidness. As one of the applications, we check whether the conformal backgrounds are preferred in some way on the classical level, with the conclusion that at this level, there is no obvious reason for such a preference, the space $S^1 \times S^3$ studied in earlier works being a special case. Some other possible properties of the higher derivative gravity given by the spectral action are briefly discussed., typos and small mistakes corrected, references added, journal version

Background Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families. Methods Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children’s Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count. Results Eleven young people (5 male, median age 13 years, range 7–16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients. Conclusions IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.

In contrast to peer-assisted learning (PAL) in clinical training, there is scant literature on the efficacy of PAL during basic medical sciences teaching for preclinical students. A group of senior medical students aimed to design and deliver clinically oriented small-group tutorials after every module in the preclinical curriculum at a United Kingdom medical school. Twenty tutorials were delivered by senior students throughout the year to first- and second-year students. A baseline questionnaire was delivered to inform the development of the program followed by an end-point questionnaire the next year ( n = 122). Quizzes were administered before and after five separate tutorials to assess changes in mean student scores. Additionally, each tutorial was evaluated via a questionnaire for participants ( n = 949). All five posttutorial quizzes showed a significant improvement in mean student score ( P < 0.05). Questionnaires showed students found the program to be relevant and useful for revision purposes and appreciated how tutorials contextualized basic science to clinical medicine. Students appreciated the interactive nature of the sessions and found receiving personalized feedback about their learning and consolidating information with someone familiar with the material to be useful. With the inclusion of the program, students felt there were now an adequate number of tutorials during the year. In conclusion, this study shows that senior medical students can design and deliver a program that adds value to the mostly lecture-based formal preclinical curriculum. We hope that our study can prompt further work to explore the effect of PAL on the teaching of basic sciences during preclinical studies.

Aim Modernisation of records, coupled with advances in informatics, is making analyses of electronic records an increasingly rich source for researchers to help form evidence-based policy and treatments. We aimed to review the public’s views on health research from electronic records and databases, with a focus on children and young people (CYP). Method A literature search on the public’s perceptions of research from health records, data linkage, and acceptability of different modes of consent. Two focus groups using semi–structured discussions, to explore young people’s perceptions of access to healthcare data, were held with our Young Person’s Advisory Group. YPAG consists of 30 12–17 year–olds from diverse socio–economic and ethnic backgrounds. Results Published research is primarily in adults. There is widespread unawareness and misunderstanding of research using health records. The public wish to be informed when their data is used for research as a matter of courtesy and to allow control of their participation. Opt-in consent was preferred. Opt-out consent is deemed potentially acceptable, with some studies demonstrating increased acceptability when participation bias is explained. Only one study explored CYP’s views (17–19 year-olds). This broadly mirrored adults’ views, including attitudes towards opt-out consent. No studies were found involving younger adolescents. Our focus groups highlighted young peoples’ strong sense of ownership of their data and desire to be informed. Acceptability of access to data varies depending on exactly what is being used, by whom and for what purpose. A high degree of precision and flexibility in permission-granting was desired, alluding to dynamic consent. A distrust in the security of their data co-existed with a misunderstanding of the protection anonymization provides. Conclusion CYP are clear in their desire for active engagement when it comes to using their data for research and show appreciation for balancing one’s privacy against the ‘greater good’ for society. Further work is needed to explore how best to inform CYP of data use, allow informed participation, tackle misconceptions and maximise their partnership in this type of research. This is required to increase researchers’ transparency and accountability with the public and maintain public trust in clinical research.

In this paper, we will analyze the gravitational collapse in the framework of gravity's rainbow. We will demonstrate that the position of the horizon for a particle inside the black hole depends on the energy of that particle. It will also be observe that the position of the horizon for a particle falling radially into the black hole also depends on its energy. Thus, it is possible for a particle coming from outside to interact with a particle inside the black, and take some information outside the black hole. This is because for both these particles the position of horizon is different. So, even though the particle from inside the black hole is in its own horizon, it is not in the horizon of the particle coming from outside. Thus, we will demonstrate that in gravity's rainbow information can get out of a black hole., Comment: accepted in Int. J. Geom. Methods Mod. Phys

This article discusses the redevelopment of a significant area of Wellington city's waterfront, centred on the Chaffers Park district between the national museum, Te Papa Tongarewa, and Oriental Bay. This site is now being transformed into Waitangi Park. The analysis seeks to determine whether or not the redevelopment will be successful, by assessing the wider context of the issue and evaluating the perspectives of stakeholders.

With the accelerating advances in technology the need to understand human-machine interactions for the purpose of enhancing cooperative activities has become an important theoretical and empirical problem. This study uses Virtual Partner Interaction (VPI) to examine how behavioral coupling between humans and humanoid robots can be modulated through the use of embedded micro gestures or small parametric noise. VPI is a behavioral dynamic clamp constructed from established principles of live two-people interaction during performance of a coordination task. The gestures are akin to “motioning” behaviors and are in the form of parametric noise applied to either the damping or the restoring term of the oscillator dynamics of the virtual partner. To increase the probability of correctly detecting and measuring the individual performances (VP vs. subject), a conflicting task is used: subjects coordinate their rhythmic movements with the VP inphase while the VP is programmed to coordinate nominally only in antiphase. Preliminary results show that that the probability of human subjects switching to the VP's preferred pattern (anti-phase) are enhanced by parametric perturbations on either the damping or the restoring term of the VP oscillator as compared to when no perturbation is applied. The results have implication on how one may enhance human-humanoid robot coordination during performance of cooperative tasks.