Reflecting the changing world of work? A critique of existing survey measures and a proposal for capturing new ways of working

In recent decades we have seen significant and varied changes in the world of work. Most prominent among these is the diminishing prevalence of the standard employment relationship. These changes challenge traditional notions of what constitute ‘employment’, ‘employers’, ‘employees’, the ‘workplace’ and the ‘working day’. Many current survey instruments are still based on the concept of the standard employment relationship, however. This article illustrates some limitations of existing conceptualisations and definitions of flexible work arrangements and of the instruments used to measure them in major surveys. It also suggests ways of tackling these limitations. The aim of highlighting potential limitations of existing survey instruments is to enable data users to be more reflective about what the results actually do and do not report, and to encourage survey designers to modify existing instruments and develop new instruments to better capture contemporary realities, including multiple jobholding and internet and platform work

Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires the activity of Lyn and Syk kinases

Activation of the B cell receptor complex in B lymphocytes causes Ca2+ release from intracellular stores, which, in turn, activates ion channels known as Icrac. We investigated the mechanisms that link Ca2+ store release to channel gating in DT40 B lymphocyte cell lines genetically manipulated to suppress the expression of several tyrosine kinases: Btk, Lyn, Syk, and the Blnk adaptor molecule. The simultaneous but not the independent suppression of Lyn and Syk expression prevents the activation of Icrac without interfering with thapsigargin-sensitive Ca2+ store release. Icrac activation by Ca2+ is reversed in mutant cells by the homologous expression of the missing kinases. Pharmacological inhibition of kinase activity by LavendustinA and PP2 cause the same functional deficit as the genetic suppression of enzyme expression. Biochemical assays demonstrate that kinase activity is required as a tonic signal: targets must be phosphorylated to link Ca2+ store release to Icrac gating. The action of kinases on Icrac activation does not arise from control of the expression level of the stromal interaction molecule 1 and Orai1 proteins

Decoherence of a Josephson qubit due to coupling to two level systems

Noise and decoherence are major obstacles to the implementation of Josephson junction qubits in quantum computing. Recent experiments suggest that two level systems (TLS) in the oxide tunnel barrier are a source of decoherence. We explore two decoherence mechanisms in which these two level systems lead to the decay of Rabi oscillations that result when Josephson junction qubits are subjected to strong microwave driving. (A) We consider a Josephson qubit coupled resonantly to a two level system, i.e., the qubit and TLS have equal energy splittings. As a result of this resonant interaction, the occupation probability of the excited state of the qubit exhibits beating. Decoherence of the qubit results when the two level system decays from its excited state by emitting a phonon. (B) Fluctuations of the two level systems in the oxide barrier produce fluctuations and 1/f noise in the Josephson junction critical current I_o. This in turn leads to fluctuations in the qubit energy splitting that degrades the qubit coherence. We compare our results with experiments on Josephson junction phase qubits.Comment: 23 pages, Latex, 6 encapsulated postscript figure

VIEWS FROM GP AND PSYCHIATRIC TRAINEES ABOUT GETTING EXPERIENCE IN EACH OTHER’S SPECIALTY DURING TRAINING: A WAY TO DEVELOP A SHARED CULTURE?

The need to deliver holistic medical care that addresses both physical and mental health requirements has never been more important. The UK medical training system has been designed to provide all medical graduates with a broad experience of different medical specialities and psychiatry prior to entering specialist training. Furthermore there is a distinct crossover between Psychiatric and General Practice training, with programmes providing trainees with the opportunity to work alongside each other in the care of mental health patients. The video presentation will explain the UK medical training system in more detail, before going on to explore how the organisation of training may foster a shared culture among different specialities and how it could form a model for improving parity of esteem of medical and physical health care. In addition it will discuss the strengths and weaknesses of this system from a trainee perspective and will conclude with comments from eminent Psychiatrists whom have special interests in medical training and developingparity of mental and physical health care

COVID-19: Social Distancing and Physical Activity in United Kingdom Residents With Visual Impairments

Introduction: The introduction of the COVID-19 lockdown and social distancing policy has the potential to restrict access to physical activity, change exercise behavior, and to increase sedentary behavior. This study was conducted with the support of British Blind Sport and evaluates the effect of the lockdown policy on adults with visual impairments in the United Kingdom (UK). Methods: An online survey based on the World Health Organization’s Global Physical Activity Questionnaire was completed by 73 participants (median age 35–44 years, 59% female) to gain information on how the implementation of the lockdown policy by the UK government has affected physical activity and sedentary behavior in adults that are visually impaired. Paired sample t-tests and Wilcoxon signed rank tests were used to analyze continuous and Likert scale data, respectively. Results: The majority of participants continued to exercise during lockdown, but the nature of this activity altered with a significant change to exercising in a private indoor space (+190% (always), z = −3.871, p < 0.001), and those exercising alone (+118% (always), z = −2.595, p = 0.009). The volume of activity reduced in all cases, between −11% and −52%, with significant changes in duration of vigorous day-to-day activity, moderate day-to-day activity, travel by foot or cycle, and vigorous recreational activity. Sedentary behavior increased on average by 21% ( t(59) = −2.050, p = 0.045), with a greater effect seen in females (+36%, t(35) = −2.525, p = 0.016). Discussion: Reductions in physical activity volume and increases in sedentary behavior are consequences of the UK lockdown for those with visual impairments. The health and well-being implications of these data to this specific population are of particular concern. Implications for Practitioners: Lockdown measures should be designed with consideration of the needs of people with disabilities. Innovative ways to engage these populations in physical activity are strongly encouraged

Primis : design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.MethodsAdults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with >= 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.ConclusionThe phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.Trial Registration: ClinicalTrials.gov NCT03890120; registered 26/03/2019.Peer reviewe

COVID-19: self-reported reductions in physical activity and increases in sedentary behaviour during the first national lockdown in the United Kingdom

Purpose The United Kingdom (UK) government imposed its first national lockdown in response to COVID-19 on the 23rd of March 2020. Physical activity and sedentary behaviour levels are likely to have changed during this period. Methods An online survey was completed by n=266 adults living within the UK. Differences in day-to-day and recreational physical activity (at moderate and vigorous intensities), travel via foot/cycle, and sedentary behaviour were compared before and during the initial COVID-19 lockdown. Results The median level of total weekly physical activity significantly reduced (− 15%, p £25,000). Conclusions Now that the UK is transitioning to a state of normal living, strategies that can help individuals gradually return to physical activities, in accordance with the 2020 WHO guidelines, are of paramount importance to reducing risks to health associated with physical inactivity and sedentary behaviour

Promoting the use of the PRECISE score for prostate MRI during active surveillance: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship

OBJECTIVES: The PRECISE criteria for serial multiparametric magnetic resonance imaging (MRI) of the prostate during active surveillance recommend the use of a dedicated scoring system (PRECISE score) to assess the likelihood of clinically significant radiological change. This pilot study assesses the effect of an interactive teaching course on prostate MRI during active surveillance in assessing radiological change in serial imaging. METHODS: Eleven radiology fellows and registrars with different experience in prostate MRI reading participated in a dedicated teaching course where they initially evaluated radiological change (based on their previous training in prostate MRI reading) independently in fifteen patients on active surveillance (baseline and follow-up scan), and then attended a lecture on the PRECISE score. The initial scans were reviewed for teaching purposes and afterwards the participants re-assessed the degree of radiological change in a new set of images (from fifteen different patients) applying the PRECISE score. Receiver operating characteristic analysis was performed. Confirmatory biopsies and PRECISE scores given in consensus by two radiologists (involved in the original draft of the PRECISE score) were the reference standard. RESULTS: There was a significant improvement in the average area under the curve (AUC) for the assessment of radiological change from baseline (AUC: 0.60 [Confidence Intervals: 0.51-0.69] to post-teaching (AUC: 0.77 [0.70-0.84]). This was an improvement of 0.17 [0.016-0.28] (p = 0.004). CONCLUSIONS: A dedicated teaching course on the use of the PRECISE score improves the accuracy in the assessment of radiological change in serial MRI of the prostate

MicroRNA clusters integrate evolutionary constraints on expression and target affinities : the miR-6/5/4/286/3/309 cluster in Drosophila

This research was supported by the Hong Kong Research Grant Council GRF Grant (14103516), The Chinese University of Hong Kong Direct Grant (4053248), and TUYF Charitable Trust (6903957) (JHLH).A striking feature of microRNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a microRNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this microRNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of microRNA cluster members were also constructed. Expression of individual microRNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient microRNAs together (miR-5/4/286/3/309) or more recently evolved clustered microRNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed down-regulation of leg patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of microRNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct microRNAs. Considered together, the microRNA targets and the evolutionary ages of each microRNA in the cluster demonstrates the importance of microRNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing microRNAs.PostprintPeer reviewe