An analytical framework for employment regulation: investigating the regulatory space

peer-reviewedPurpose – The purpose of this paper is to advance a conceptual analytical framework to help explain employment regulation as a dynamic process shaped by institutions and actors. The paper builds on and advances regulatory space theory. Design/methodology/approach – The paper analyses the literature on regulatory theory and engages with its theoretical development. Findings – The paper advances the case for a broader and more inclusive regulatory approach to better capture the complex reality of employment regulation. Further, the paper engages in debates about the complexity of employment regulation by adopting a multi-level perspective. Research limitations/implications – The research proposes an analytical framework and invites future empirical investigation. Originality/value – The paper contends that existing literature affords too much attention to a (false) regulation vs deregulation dichotomy, with insufficient analysis of other “spaces” in which labour policy and regulation are formed and re-formed. In particular, the proposed framework analyses four different regulatory dimensions, combining the legal aspects of regulation with self-regulatory dimensions of employment regulatio.ACCEPTEDpeer-reviewe

Fishers and fisheries of Moreton Bay

Moreton Bay is one of the most intensely used coastal systems in Australia and supports some of Queensland’s most productive fisheries, including Indigenous, commercial, recreational and charter sectors. This paper explores the economic and cultural value of these fisheries to the Moreton Bay region and the challenges they face. Fishing is recognised as one of Queensland’s oldest industries. Marine resources were harvested by Indigenous peoples long before European settlement and continue to form an important part of Indigenous culture today. Commercial fisheries operating within Moreton Bay are valued at $24m per annum, and target a variety of species groups including prawns, crabs, squid and finfish such as mullet, bream and whiting. Direct expenditure by the recreational sector in Moreton Bay is estimated to be ~$194m per annum, with fishers harvesting mud crabs, sand whiting, snapper, tailor and bream, among others. Despite the longevity of these sectors, a number of challenges exist. These include managing risks related to climate change, a growing urban population, and the need to mitigate environmental impacts from fishing and other marine activities. Interactions with other management sectors, including marine park planning and native title rights, will also need to evolve if we are to ensure a sustainable future for the fisheries of Moreton Bay

Towards a new paradigm of care: the International Declaration on Youth Mental Health.

A recent and growing body of evidence on young people\u27s mental health has pointed to the need for an international response to the increasing and concerning rates of mental ill-health among young people.[1, 2] The periods of adolescence and emerging adulthood[3] are considered the peak periods for the onset of mental ill-health[4] with 75% of all adult diagnoses of mental ill-health having had an onset before the age of 25 years.[5] In an era when the physical health of young people has never been better,[6] their psychological and mental health has never been worse.[7] This leaves young people vulnerable to developing potentially intractable and enduring mental health difficulties with the inevitable personal, familial, social and vocational consequences that accompany the experience of mental ill-health.[4, 8] In spite of growing concerns about young people\u27s mental health, service provision for young people remains largely inadequate and unsuited to their needs. A number of systemic factors can be implicated in insufficient and unsuitable mental health service provision for young people. Internationally, there has been an endemic failure to invest in mental health across the lifespan with an average global spend on mental health of less than $US3 per capita per year.[9] This global underinvestment brings with it particular challenges in relation to the level of priority afforded to youth mental health and the concurrent commitment needed to respond to the scale of young people\u27s mental health needs. Even in developed countries where mental health services exist, there are widespread problems with services targeting young people. Primary care and other front line community agencies can struggle to respond to high levels of need, often with little support from specialist mental health services. Specialist mental health services have traditionally followed a paediatric-adult split, with child and adolescent services offering intervention until the largely arbitrary ages of 16 or 18 years and adult services taking all young people 18 years and older.[1] In many instances, there have been gaps in service provision between the ages of 16 and 18 years.[10] This has resulted in many young people being unable to access specialist mental health support during these critical years along with high rates of attrition and dissatisfaction by young people during this transitional period.[11, 12] With a recognition that, in many sociocultural contexts, the transition from adolescence to adulthood is a variable one that spans a period from the mid-teens to the mid- to late-20s,[13] both young people and youth mental health advocates have called for a reorganization of mental health services to mirror this extended developmental period for young people.[2] Not surprisingly, there has been a trend of poor help seeking and engagement by young people in mental health services.[14, 15] A key challenge remains in supporting young people to reach out for help when they need it and early evidence suggests that factors such as ease of access, the physical environment, location, atmosphere, branding and peer influence can promote help seeking among young people.[12] It must be noted, however, that even when services are youth friendly and appropriate to their needs, individual and psychological factors strongly influence help-seeking behaviour among young people experiencing emotional or psychological distress.[16, 17] From both an economic[18] and a human impact perspective, there is a strong rationale to invest in efforts to tackle the reality of mental ill-health among the youth population.[2] Efforts to establish a new youth mental health paradigm have already begun and are gaining momentum internationally, reflected most recently in the establishment of a new International Association for Youth Mental Health (http://www.iaymh.org). The first International Youth Mental Health Conference was held in Melbourne, Australia, in 2010 and the second is being held in 2013 in Brighton, the UK (http://www.iaymh2013.com). Those involved in the youth mental health movement recognize that positively impacting on young people\u27s mental health trajectories requires transformative change. Along with a need for early promotion, detection and intervention, stemming the tide of mental ill-health among young people requires a fundamental change in how we think about young people and their mental health. It demands that we challenge traditional approaches to service development and delivery and replace them with approaches that are inclusive and empowering for young people and their families. Young people and their families need to be involved in designing and implementing more creative, responsive, accessible and youth-friendly mental health services that have the capacity to meet their needs

Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU)

BackgroundPrevious studies have revealed the role of dysregulated urokinase plasminogen activator (encoded by PLAU) expression and activity in several pathways associated with cancer progression. However, systematic investigation into the association of PLAU expression with factors that modulate PDAC (pancreatic ductal adenocarcinoma) progression is lacking, such as those affecting stromal (pancreatic stellate cell, PSC)-cancer cell interactions, tumour immunity, PDAC subtypes and clinical outcomes from potential PLAU inhibition.MethodsThis study used an integrated bioinformatics approach to identify prognostic markers correlated with PLAU expression using different transcriptomics, proteomics, and clinical data sets. We then determined the association of dysregulated PLAU and correlated signatures with oncogenic pathways, metastatic phenotypes, stroma, immunosuppressive tumour microenvironment (TME) and clinical outcome. Finally, using an in vivo orthotopic model of pancreatic cancer, we confirmed the predicted effect of inhibiting PLAU on tumour growth and metastasis.ResultsOur analyses revealed that PLAU upregulation is not only associated with numerous other prognostic markers but also associated with the activation of various oncogenic signalling pathways, aggressive phenotypes relevant to PDAC growth and metastasis, such as proliferation, epithelial-mesenchymal transition (EMT), stemness, hypoxia, extracellular cell matrix (ECM) degradation, upregulation of stromal signatures, and immune suppression in the tumour microenvironment (TME). Moreover, the upregulation of PLAU was directly connected with signalling pathways known to mediate PSC-cancer cell interactions. Furthermore, PLAU upregulation was associated with the aggressive basal/squamous phenotype of PDAC and significantly reduced overall survival, indicating that this subset of patients may benefit from therapeutic interventions to inhibit PLAU activity. Our studies with a clinically relevant orthotopic pancreatic model showed that even short-term PLAU inhibition is sufficient to significantly halt tumour growth and, importantly, eliminate visible metastasis.ConclusionElevated PLAU correlates with increased aggressive phenotypes, stromal score, and immune suppression in PDAC. PLAU upregulation is also closely associated with the basal subtype type of PDAC; patients with this subtype are at high risk of mortality from the disease and may benefit from therapeutic targeting of PLAU

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure : An Exploratory Proof-of-Concept Trial

Acknowledgments We would like to extend our sincerest gratitude to all the colleagues and hospital staff who worked tirelessly throughout the pandemic and without whom this work would not have been possible. Firstly, we would like to thank our colleagues in the intensive care unit (ICU), in particular the matrons, Sean Carroll and Sinead Hanton, and research nurses, Filipe Helder and Amitaa Maharajh for their support, and bedside nurses who bore the responsibility of drug administration. We would also like to extend our thanks to ICU consultants who acted as professional legal consultees on behalf of critical care patients. Equally, we would like to thank colleagues within the respiratory team. Their expertise was instrumental to our role in treating patients on 8N and 8E wards. A special mention to lead Nurse Mary Emerson; we were grateful for her knowledge, support and for facilitating the training for the nebulizer and drug administration on the wards. We would like to thank Aarti Nandani and all the staff in the Royal Free clinical trials pharmacy for their immense support throughout the whole pandemic, especially considering their ever-increasing workload at the time. Thanks also to the HSL coagulation laboratory, the Trust R&D department and all the staff working to cover during a very challenging time. We are also very grateful to the Royal Free charity for funding this study. Finally, we would like to thank all the clinical nurses, physiotherapists, research data managers and healthcare professionals within the Haemophilia department (and wider hospital) for all their many efforts in supporting this study. This trial was overseen by an independent data monitoring committee, chaired by Najib Rahman, Director of the Oxford Respiratory Trials Unit, University of Oxford and comprises the following committee members: Mike Makris, Jonathan Silversides and Henry Watson. Funding Royal Free Charity Trust Fund 35 provided funding for this study. The study drug was provided by Boehringer Ingelheim (BI). BI had no role in the design, analysis, or interpretation of the results. They were given the opportunity to review the manuscript for medical and scientific accuracy since it relates to BI substances and intellectual property considerations.Peer reviewedPublisher PD

De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations

Purpose: ZMYND8 encodes a multidomain protein that serves as a central interactive hub for coordinating critical roles in transcription regulation, chromatin remodeling, regulation of superenhancers, DNA damage response and tumor suppression. We delineate a novel neurocognitive disorder caused by variants in the ZMYND8 gene. Methods: An international collaboration, exome sequencing, molecular modeling, yeast twohybrid assays, analysis of available transcriptomic data and a knockdown Drosophila model were used to characterize the ZMYND8 variants. Results: ZMYND8 variants were identified in 11 unrelated individuals; 10 occurred de novo and one suspected de novo; 2 were truncating, 9 were missense, of which one was recurrent. The disorder is characterized by intellectual disability with variable cardiovascular, ophthalmologic and minor skeletal anomalies. Missense variants in the PWWP domain of ZMYND8 abolish the interaction with Drebrin and missense variants in the MYND domain disrupt the interaction with GATAD2A. ZMYND8 is broadly expressed across cell types in all brain regions and shows highest expression in the early stages of brain development. Neuronal knockdown of the Drosophila ZMYND8 ortholog results in decreased habituation learning, consistent with a role in cognitive function. Conclusion: We present genomic and functional evidence for disruption of ZMYND8 as a novel etiology of syndromic intellectual disability