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The North Sea is one of the most studied and exploited ecosystems worldwide. The multiple uses from industrial, transport, as well as recreational activities have required researchers, regulators, and legislators to understand and, where possible, to minimize any expected negative environmental impacts. As with any international sea, assessing the current pressures and management actions resulting from these activities is centred on several national and international legislative instruments. This variety of co-existing legislations makes development processes and regulatory assessments cumbersome and time consuming. Hence there is a need to integrate environmental risk assessment and management across sectors, ensuring smart, cost-effective data generation, as well as supporting and standardizing environmental practices. This paper provides an overview of the changing regulatory frameworks regarding offshore chemicals used in the oil and gas industry, and the process of chemical risk assessment conducted under the Offshore Chemical Notification Scheme (ONCS) in the UK. Our view of methodological, research, and regulatory needs and challenges that should be addressed to ensure an adequate and sustainable assessment of offshore chemical use in the North Sea is discussed. Furthermore, we discuss the issues faced regarding chemicals used in the UK oil and gas sector with respect to declining hydrocarbon production. [ABSTRACT FROM AUTHOR]

Background Incidence of CTEPH following idiopathic PE has been reported as 4%. The British Thoracic Society recommends that patients with massive or submassive PE should undergo echocardiography 6-12 weeks following the index event. Aim To investigate local practice in the follow-up of patients with acute PE to devise management guidelines. Methods A retrospective study of 110 patients diagnosed with acute PE at our hospital between 2007 and 2008 was conducted. Mean age was 68.6 years (range 27-100), 40 (36%) were male and 18 (16%) had previous venous thromboembolism. In 51 (46%) patients PE was idiopathic. Results All patients diagnosed with PE were normotensive and 27 (25%) had in-patient echocardiography (ECHO). In 5 (18%) patients scan confirmed RV dilatation and 2 of them had repeated ECHO within 2 months. Subsequently one patient was diagnosed with CTEPH and underwent pulmonary endarterectomy. In the group of patients with acute PE but without in-patient echocardiography 40 of 83 (48%) received a follow-up appointment (mean 4 months) and 10 (25%) had follow-up ECHO. Two more patients were diagnosed with CTEPH during this period (mean 34 months) with an overall incidence of 2.9%. Conclusion Recorded outcome, literature review and the BTS/ERS guidelines resulted in the development of local protocol for the screening acute PE survivors for CTEPH. [Abstract P7 figure 1]. [ABSTRACT FROM AUTHOR]

Abstract Background Haematopoiesis is a process of formation of mature blood cells from hematopoietic progenitors in bone marrow. Haematopoietic progenitors are stimulated by growth factors and cytokines to proliferate and differentiate, and they die via apoptosis when these factors are depleted. An aberrant response to growth environment may lead to haematological disorders. Bomapin (serpinb10) is a hematopoietic- and myeloid leukaemia-specific protease inhibitor with unknown function. Results We found that the majority of naturally expressed bomapin was located in the nucleus. Both the natural and recombinant bomapin had a disulfide bond which linked the only two bomapin cysteines: one located in the CD-loop and the other near the C-terminus. Computer modelling showed that the cysteines are distant in the reduced bomapin, but can easily be disulfide-linked without distortion of the overall bomapin structure. Low-level ectopic expression of bomapin in bomapin-deficient K562 cells resulted in about 90% increased cell proliferation under normal growth conditions. On the other hand, antisense-downregulation of natural bomapin in U937 cells resulted in a decreased cell proliferation. Bomapin C395S mutant, representing the reduced form of the serpin, had no effect on cell proliferation, suggesting that the disulfide bond-linked conformation of bomapin is biologically important. The bomapin-dependent effect was specific for myeloid cells, since ectopic expression of the serpin in HT1080 cells did not change cell proliferation. In contrast to the survival-promoting activity of bomapin in cells cultured under optimal growth conditions, bomapin enhanced cell apoptosis following growth factor withdrawal. Conclusions We propose that bomapin is a redox-sensitive nuclear serpin that augments proliferation or apoptosis of leukaemia cells, depending on growth factors availability.

UDP-glucose (UDPG) pyrophosphorylase (UGPase) catalyzes a reversible reaction, producing UDPG, which serves as an essential precursor for hundreds of glycosyltransferases in all organisms. In this study, activities of purified UGPases from sugarcane and barley were found to be reversibly redox modulated in vitro through oxidation by hydrogen peroxide or oxidized glutathione (GSSG) and through reduction by dithiothreitol or glutathione. Generally, while oxidative treatment decreased UGPase activity, a subsequent reduction restored the activity. The oxidized enzyme had increased K m values with substrates, especially pyrophosphate. The increased K m values were also observed, regardless of redox status, for UGPase cysteine mutants (Cys102Ser and Cys99Ser for sugarcane and barley UGPases, respectively). However, activities and substrate affinities ( K m s) of sugarcane Cys102Ser mutant, but not barley Cys99Ser, were still prone to redox modulation. The data suggest that plant UGPase is subject to redox control primarily via changes in the redox status of a single cysteine. Other cysteines may also, to some extent, contribute to UGPase redox status, as seen for sugarcane enzymes. The results are discussed with respect to earlier reported details of redox modulation of eukaryotic UGPases and regarding the structure/function properties of these proteins., Competing Interests: The authors declare no conflict of interest.

Objectives: We assessed authors' language and methods to determine alignment between reported aims, methods, intent, and interpretations in observational studies in spinal pain or osteoarthritis., Study Design and Setting: We searched five databases for observational studies that included people with spinal pain or osteoarthritis published in the last 5 years. We randomized 100 eligible studies, and classified study intent (aims and methods) and interpretations as causal, non-causal, unclear, or misaligned., Results: Overall, 38% of studies were aligned regarding their intent and interpretation (either causally (22%) or non-causally (16%)). 29% of studies' aims and 29% of study methods were unclear. Intent was misaligned in 16% of studies (where aim differed to method) and 23% of studies had misaligned interpretations (where there were multiple conflicting claims). The most common kind of aim was non-causal (38%), and the most common type of method (39%), intent (38%), and interpretations (35%) was causal., Conclusions: Misalignment and mixed messages are common in observational research of spinal pain and osteoarthritis. More than 6 in 10 observational studies may be uninterpretable, because study intent and interpretations do not align. While causal methods and intent are most common in observational research, authors commonly shroud causal intent in non-causal terminology., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Participation in regular physical activity has significant physical, psychological, and social benefits, including the prevention and treatment of Type 2 Diabetes (T2D). The primary aim of this paper was to evaluate the impact of theeCoFit physical activity intervention on depression and anxiety symptoms among adults at risk of, or diagnosed with, T2D. The primary outcomes were assessed using Patient Health Questionnaire-9, and Generalised Anxiety Disorder-7. The secondary aim was to test for the potential mediators for the intervention effect on mental health. The 20-week intervention was evaluated using a two-arm randomised controlled trial with await list control group. The intervention included two phases: Phase 1 integrated group face-to-face sessions and the use of the eCoFit smartphone application (app); and Phase 2 that included the use of the app only. Participants (n = 84) were assessed at baseline and 10- and 20-weeks post-baseline. Social support, self-efficacy, nature-relatedness, and perceived sleep quality were examined as potential mechanisms for the intervention effects on mental health. A significant interaction for depression severity was observed at 20-weeks (-1.76, CI -3.48, -05, p= .044, d= -0.35). There were no significant intervention effects for anxiety or any of the potential mechanisms.

People living with mental health conditions experience a significantly reduced life expectancy compared to people without, largely linked to health risk behaviours and associated chronic disease. Community managed organisations (CMOs) represent an important setting in which to address health risk behaviours among people with mental health conditions. However, little is known about how these behaviours (smoking, poor nutrition, alcohol consumption, inadequate physical activity, poor sleep: SNAPS) are being addressed in this setting. One-on-one, semi-structured telephone interviews were conducted with a sample of 12 senior staff, representing 12 CMOs in New South Wales, Australia to: (1) explore types of support provided by CMOs to address the SNAPS behaviours of consumers living with a mental health condition; and (2) assess perceived organisational and staff level barriers and facilitators to providing such support. Transcribed interviews were analysed using inductive thematic analysis. This study found there was a range of supports offered by CMOs, and these differed by health risk behaviour. Findings suggest CMOs are well-placed to embed SNAPS supports as a part of their service provision; however, available funding, consistency of supports, workplace policies and culture, collaboration with other available supports, staff training and education, all impacted capacity.

People living with mental health conditions have a reduced life expectancy of approximately 10 years compared to the general population, largely due to physical chronic diseases and higher rates of tobacco smoking, poor nutrition, harmful alcohol consumption, physical inactivity and poor sleep behaviours. Community managed organisations (CMOs) may play a valuable role in providing preventive care to people with mental health conditions (consumers) to address these health behaviours. This paper reports the findings of a cross-sectional survey undertaken between November 2018 and February 2019 with leaders of CMOs (n = 76) that support people with mental health conditions in the state of New South Wales, Australia to: 1) measure the provision of preventive care (screening, support, and connections to specialist services) for five health behaviours; 2) identify the presence of key organisational features (e.g., data collection, staff training); and 3) explore if these organisational features were associated with the provision of preventive care. Preventive care provision to a majority of consumers (50% or more) was least frequently reported for tobacco smoking and most frequently reported for physical activity. Staff training and guidelines regarding the provision of preventive care were associated with the provision of such care. The results demonstrate that CMOs are already engaged in providing preventive care to some extent, with certain behaviours and preventive care elements addressed more frequently than others. Further research with additional CMO stakeholders, including staff and consumers, is needed to gain a deeper understanding of factors that may underlie CMOs capacity to routinely provide preventive care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: ecofit is an evidence-based multi-component physical activity intervention that integrates smartphone technology, the outdoor environment, and social support. In a previous efficacy trial, significant improvements were found across several clinical, fitness, and mental health outcomes among adults at risk of (or with) type 2 diabetes., Methods: The aim of the present pilot study was to evaluate a number of patient-centered and feasibility outcomes of the ecofit intervention in a "real-world" setting, using a scalable implementation model. ecofit was adapted and implemented by a rural municipal council in the Upper Hunter Shire, New South Wales, Australia, and evaluated using a single-group pre-post design. Inactive middle-aged and older adults (N=59) were recruited and assessed at 6 (primary time-point) and 20 weeks (follow-up)., Results: Improvements were found in this predominantly overweight and obese sample for aerobic fitness, functional mobility, upper and lower body muscular fitness, systolic blood pressure, and waist circumference at 6 weeks. At 20 weeks, effects were found for aerobic fitness, functional mobility, upper and lower body muscular fitness, and systolic blood pressure. Overall, participants were satisfied with the ecofit program. Participants attended the 6-week primary time-point (66.1%) and follow-up at 20 weeks (41.6%)., Conclusions: Our findings support the preliminary effectiveness and feasibility of the ecofit intervention delivered by municipal council staff following a brief training from the research team. This study provides valuable preliminary evidence to support a larger implementation trial.

The ability of cells to promote plasminogen activation on their surfaces is now well recognized, and several distinct cell surface proteins have been demonstrated to function as plasminogen receptors. Here, we review studies demonstrating that plasminogen bound to cells, in addition to plasminogen directly bound to fibrin, plays a major role in regulating fibrin surveillance. We focus on the ability of specific plasminogen receptors on eukaryotic cells to promote fibrinolysis in the in vivo setting by reviewing data obtained predominantly in murine models. Roles for distinct plasminogen receptors in fibrin surveillance in intravascular fibrinolysis, immune cell recruitment in the inflammatory response, wound healing, and lactational development are discussed.

Wound healing is a complex physiologic process that proceeds in overlapping, sequential steps. Plasminogen promotes fibrinolysis and potentiates the inflammatory response during wound healing. We have tested the hypothesis that the novel plasminogen receptor, Plg-R KT , regulates key steps in wound healing. Standardized burn wounds were induced in mice and time dependence of wound closure was quantified. Healing in Plg-R KT -/- mice was significantly delayed during the proliferation phase. Expression of inflammatory cytokines was dysregulated in Plg-R KT -/- wound tissue. Consistent with dysregulated cytokine expression, a significant delay in wound healing during the proliferation phase was observed in mice in which Plg-R KT was specifically deleted in myeloid cells. Following wound closure, the epidermal thickness was less in Plg-R KT -/- wound tissue. Paradoxically, deletion of Plg-R KT , specifically in keratinocytes, significantly accelerated the rate of healing during the proliferation phase. Mechanistically, only two genes were upregulated in Plg-R KT -/- compared with Plg-R KT +/+ wound tissue, filaggrin, and caspase 14. Both filaggrin and caspase 14 promote epidermal differentiation and decrease proliferation, consistent with more rapid wound closure and decreased epidermal thickness during the remodeling phase. Fibrin clearance was significantly impaired in Plg-R KT -/- wound tissue. Genetic reduction of fibrinogen levels to 50% completely abrogated the effect of Plg-R KT deletion on the healing of burn wounds. Remarkably, the effects of Plg-R KT deletion on cytokine expression were modulated by reducing fibrinogen levels. In summary, Plg-R KT is a new regulator participating in different phases of cutaneous burn wound healing, which coordinately plays a role in the interrelated responses of inflammation, keratinocyte migration, and fibrinolysis.

Background: Reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global priority. Contact tracing identifies people who were recently in contact with an infected individual, in order to isolate them and reduce further transmission. Digital technology could be implemented to augment and accelerate manual contact tracing. Digital tools for contact tracing may be grouped into three areas: 1) outbreak response; 2) proximity tracing; and 3) symptom tracking. We conducted a rapid review on the effectiveness of digital solutions to contact tracing during infectious disease outbreaks., Objectives: To assess the benefits, harms, and acceptability of personal digital contact tracing solutions for identifying contacts of an identified positive case of an infectious disease., Search Methods: An information specialist searched the literature from 1 January 2000 to 5 May 2020 in CENTRAL, MEDLINE, and Embase. Additionally, we screened the Cochrane COVID-19 Study Register., Selection Criteria: We included randomised controlled trials (RCTs), cluster-RCTs, quasi-RCTs, cohort studies, cross-sectional studies and modelling studies, in general populations. We preferentially included studies of contact tracing during infectious disease outbreaks (including COVID-19, Ebola, tuberculosis, severe acute respiratory syndrome virus, and Middle East respiratory syndrome) as direct evidence, but considered comparative studies of contact tracing outside an outbreak as indirect evidence. The digital solutions varied but typically included software (or firmware) for users to install on their devices or to be uploaded to devices provided by governments or third parties. Control measures included traditional or manual contact tracing, self-reported diaries and surveys, interviews, other standard methods for determining close contacts, and other technologies compared to digital solutions (e.g. electronic medical records)., Data Collection and Analysis: Two review authors independently screened records and all potentially relevant full-text publications. One review author extracted data for 50% of the included studies, another extracted data for the remaining 50%; the second review author checked all the extracted data. One review author assessed quality of included studies and a second checked the assessments. Our outcomes were identification of secondary cases and close contacts, time to complete contact tracing, acceptability and accessibility issues, privacy and safety concerns, and any other ethical issue identified. Though modelling studies will predict estimates of the effects of different contact tracing solutions on outcomes of interest, cohort studies provide empirically measured estimates of the effects of different contact tracing solutions on outcomes of interest. We used GRADE-CERQual to describe certainty of evidence from qualitative data and GRADE for modelling and cohort studies., Main Results: We identified six cohort studies reporting quantitative data and six modelling studies reporting simulations of digital solutions for contact tracing. Two cohort studies also provided qualitative data. Three cohort studies looked at contact tracing during an outbreak, whilst three emulated an outbreak in non-outbreak settings (schools). Of the six modelling studies, four evaluated digital solutions for contact tracing in simulated COVID-19 scenarios, while two simulated close contacts in non-specific outbreak settings. Modelling studies Two modelling studies provided low-certainty evidence of a reduction in secondary cases using digital contact tracing (measured as average number of secondary cases per index case - effective reproductive number (R eff )). One study estimated an 18% reduction in R eff with digital contact tracing compared to self-isolation alone, and a 35% reduction with manual contact-tracing. Another found a reduction in R eff for digital contact tracing compared to self-isolation alone (26% reduction) and a reduction in R eff for manual contact tracing compared to self-isolation alone (53% reduction). However, the certainty of evidence was reduced by unclear specifications of their models, and assumptions about the effectiveness of manual contact tracing (assumed 95% to 100% of contacts traced), and the proportion of the population who would have the app (53%). Cohort studies Two cohort studies provided very low-certainty evidence of a benefit of digital over manual contact tracing. During an Ebola outbreak, contact tracers using an app found twice as many close contacts per case on average than those using paper forms. Similarly, after a pertussis outbreak in a US hospital, researchers found that radio-frequency identification identified 45 close contacts but searches of electronic medical records found 13. The certainty of evidence was reduced by concerns about imprecision, and serious risk of bias due to the inability of contact tracing study designs to identify the true number of close contacts. One cohort study provided very low-certainty evidence that an app could reduce the time to complete a set of close contacts. The certainty of evidence for this outcome was affected by imprecision and serious risk of bias. Contact tracing teams reported that digital data entry and management systems were faster to use than paper systems and possibly less prone to data loss. Two studies from lower- or middle-income countries, reported that contact tracing teams found digital systems simpler to use and generally preferred them over paper systems; they saved personnel time, reportedly improved accuracy with large data sets, and were easier to transport compared with paper forms. However, personnel faced increased costs and internet access problems with digital compared to paper systems. Devices in the cohort studies appeared to have privacy from contacts regarding the exposed or diagnosed users. However, there were risks of privacy breaches from snoopers if linkage attacks occurred, particularly for wearable devices., Authors' Conclusions: The effectiveness of digital solutions is largely unproven as there are very few published data in real-world outbreak settings. Modelling studies provide low-certainty evidence of a reduction in secondary cases if digital contact tracing is used together with other public health measures such as self-isolation. Cohort studies provide very low-certainty evidence that digital contact tracing may produce more reliable counts of contacts and reduce time to complete contact tracing. Digital solutions may have equity implications for at-risk populations with poor internet access and poor access to digital technology. Stronger primary research on the effectiveness of contact tracing technologies is needed, including research into use of digital solutions in conjunction with manual systems, as digital solutions are unlikely to be used alone in real-world settings. Future studies should consider access to and acceptability of digital solutions, and the resultant impact on equity. Studies should also make acceptability and uptake a primary research question, as privacy concerns can prevent uptake and effectiveness of these technologies., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Compared with standard wines, low-alcohol wines may have several social and health benefits. Innovative production processes have led to high-quality light wines. It is, however, unclear how consumers perceive and consume these alcohol-reduced wines. The current study aimed to investigate how people evaluate low-alcohol wine (Sauvignon Blanc) and if the reduction in alcohol and the information that a wine is low in alcohol influences consumption., Design: Randomised controlled trial (RCT)., Setting: Participants were invited to a wine tasting and randomised into one of the three conditions: they either tasted a 'new white wine' (12·5 % alcohol content), a 'new low-alcohol white wine' (8·0 % alcohol content) or they tasted the low-alcohol wine but were not aware that the wine was reduced in alcohol (low-alcohol, blinded)., Participants: Ninety participants (42 % male, mean age = 41 (sd 14) years)., Results: Mean comparisons showed similar ratings for the low-alcohol conditions and the standard alcohol condition (mean > 5·6/7). The mean consumed amount across all conditions did not differ (162 (sd 71) ml, (F2,86 = 0·43, P > 0·05)), hence people who tasted the low-alcohol wine consumed approximately 30 % less alcohol. However, participants were willing to pay more for the normal wine compared with the low-alcohol wine, (F2,87 = 3·14, P < 0·05)., Conclusions: Participants did not alter their drinking behaviour in response to the reduced alcohol content, and the low-alcohol wine was perceived positively. There might be an emerging market potential for wine of reduced alcohol content, but consumers may not be willing to pay the same price as for the standard wine.