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Mitophagy must be carefully regulated to ensure that cells maintain appropriate numbers of functional mitochondria. The SCFFBXL4 ubiquitin ligase complex suppresses mitophagy by controlling the degradation of BNIP3 and NIX mitophagy receptors, and FBXL4 mutations result in mitochondrial disease as a consequence of elevated mitophagy. Here, we reveal that the mitochondrial phosphatase PPTC7 is an essential cofactor for SCFFBXL4-mediated destruction of BNIP3 and NIX, suppressing both steady-state and induced mitophagy. Disruption of the phosphatase activity of PPTC7 does not influence BNIP3 and NIX turnover. Rather, a pool of PPTC7 on the mitochondrial outer membrane acts as an adaptor linking BNIP3 and NIX to FBXL4, facilitating the turnover of these mitophagy receptors. PPTC7 accumulates on the outer mitochondrial membrane in response to mitophagy induction or the absence of FBXL4, suggesting a homoeostatic feedback mechanism that attenuates high levels of mitophagy. We mapped critical residues required for PPTC7-BNIP3/NIX and PPTC7-FBXL4 interactions and their disruption interferes with both BNIP3/NIX degradation and mitophagy suppression. Collectively, these findings delineate a complex regulatory mechanism that restricts BNIP3/NIX-induced mitophagy.

BACKGROUND: Women seeking a vaginal birth after a caesarean section (VBAC) frequently want to keep their subsequent labour and birth free from intervention. Water immersion (WI) during labour is potentially an effective tool for women having a VBAC for its natural pain-relieving properties. However, negotiating access to WI can be difficult, especially in the context of VBAC. AIM: To explore women's experiences of negotiating WI for labour and birth in the context of VBAC. METHODOLOGY: This Grounded Theory study followed Strauss and Corbin's framework and analytic process. Twenty-five women planning or using WI for their VBAC labour or birth were recruited from two midwifery practices and a social media group across Australia. Participants were interviewed during pregnancy and/or postnatally. FINDINGS: 'Taking the reins', the core category explaining the women's experiences of assuming authority over their birth, comprised five categories: 'Robbed of my previous birth experience'; 'My eyes were opened'; 'Water is my tool for a successful VBAC'; 'Actioning my choices and rights for WI', and 'Empowered to take back control'. 'Wanting natural and normal' was the driving force behind women's desire to birth vaginally. Two mediating factors: Having someone in your corner and Rules for birth facilitated or hindered their birth choices, respectively. CONCLUSION: The women became active participants in their healthcare by seeking information and options to keep their birth experience natural and normal. Support from other women and advocacy in the form of continuity of midwifery care was crucial in successfully negotiating WI for their VBAC when navigating the complex health system.

BACKGROUND: It is widely accepted that intellectual property legal requirements such as patents and data exclusivity can affect access to medicines, but to date there has not been a comprehensive review of the empirical evidence on this topic. The World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires Member States to implement minimum standards of intellectual property protection including patents for pharmaceutical products, but also contains 'flexibilities' designed to address barriers to access to medicines. National intellectual property laws can also include TRIPS-plus rules that go beyond what is required by TRIPS. We aimed to systematically review literature that measures the impact of intellectual property rules on access to medicines, whether implemented as a result of TRIPS, TRIPS-plus provisions in other trade agreements, or unilateral policy decisions. METHODS: We searched Proquest, SCOPUS, Web of Science, PubMed, JSTOR, Westlaw and Lexis Nexis. Peer reviewed articles, government reports and other grey literature were included. Articles were eligible for inclusion if they were quantitative, in English, included a measure of cost, price, availability of or access to medicines, were about intellectual property or data exclusivity rules and published between January 1995 and October 2020. Ninety-one studies met our inclusion criteria. We systematically reviewed the studies' findings and evaluated their quality using a modified quality assessment template. RESULTS AND CONCLUSION: Five broad overarching themes and 11 subthemes were identified based on the articles' foci. They were: trade agreements (divided into EU FTAs and those that include the USA); use of TRIPS flexibilities (divided into compulsory licencing and parallel importation); patent expiry/generic entry/generic pathway (divided into comparative studies and single country studies); patent policies (also divided into comparative studies and

Bio‐logging data obtained by tagging animals are key to addressing global conservation challenges. However, the many thousands of existing bio‐logging datasets are not easily discoverable, universally comparable, nor readily accessible through existing repositories and across platforms, slowing down ecological research and effective management. A set of universal standards is needed to ensure discoverability, interoperability and effective translation of bio‐logging data into research and management recommendations. We propose a standardisation framework adhering to existing data principles (FAIR: Findable, Accessible, Interoperable and Reusable; and TRUST: Transparency, Responsibility, User focus, Sustainability and Technology) and involving the use of simple templates to create a data flow from manufacturers and researchers to compliant repositories, where automated procedures should be in place to prepare data availability into four standardised levels: (a) decoded raw data, (b) curated data, (c) interpolated data and (d) gridded data. Our framework allows for integration of simple tabular arrays (e.g. csv files) and creation of sharable and interoperable network Common Data Form (netCDF) files containing all the needed information for accuracy‐of‐use, rightful attribution (ensuring data providers keep ownership through the entire process) and data preservation security. We show the standardisation benefits for all stakeholders involved, and illustrate the application of our framework by focusing on marine animals and by providing examples of the workflow across all data levels, including filled templates and code to process data between levels, as well as templates to prepare netCDF files ready for sharing. Adoption of our framework will facilitate collection of Essential Ocean Variables (EOVs) in support of the Global Ocean Observing System (GOOS) and inter‐governmental assessments (e.g. the World Ocean Assessment), and will provide a starting point for broader

Alcohol use is a leading risk factor for death and disability, responsible for 3 million deaths in 2016. The alcohol industry is a powerful player in shaping trade and investment rules in ways that can constrain the ability of governments to regulate alcoholic beverages to reduce harm. This paper analyses publicly available submissions about alcohol in the context of Australia’s free trade agreements to determine the key themes put forward by industry.

This research report describes borehole geophysical and passive seismic surveys done at the Colchester Northern Gateway (CNG) geothermal district heat network and housing development in Essex, UK, between 10-13 February 2020. The first part of the report introduces the project context, the second part describes survey methods, and the third presents the ‘baseline survey’ results and stratigraphic interpretation. The final section summarises the key learnings, relevance of the findings to future geothermal district heating schemes in the Chalk and London Basin, and makes some recommendations for follow-up monitoring research. Five recently drilled production/injection boreholes at CNG were logged with Calliper, Temperature and Conductivity, Natural Gamma, Optical Televiewer (OPTV) tools. Some of the holes also had Resistivity and Impeller flow tools run but results were inconclusive. A site-wide Tromino H/V passive seismic survey was acquired to characterise the resonant frequency of the subsoils between the boreholes, to aid stratigraphic correlation, profile the concealed chalk ‘rockhead’ surface (i.e. depth of bedrock aquifer), and look for any evidence of the presence of faults/fracture zone, and characterise the thickness of karst and weathering profiles. The main geological formation boundaries were identified based on a combination of interpretation of Natural Gamma logs and correlation of sedimentary features observed in the OPTV images. The eroded top of the Newhaven Chalk is around 72 m below ground level (-24 m OD) in all five boreholes (BH1-5). The high-resolution OPTV images provide rich visual information on the fracture state of the upper ‘productive’ part of the chalk aquifer. A notable feature in BH4 is an 18 m long NW-SE orientated open vertical fracture that persists through the Newhaven Chalk but terminates at the top of the Seaford Chalk. The OPTV data also aids identification of key litho-stratigraphic marker horizons, such as tabular flint band

Background: Trade and investment agreements negotiated after the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) have included increasingly elevated protection o

© 2015 Australian College of Midwives. Background: There is a growing body of evidence to show that the birth environment can influence women's experiences of labour and birth as well as midwifery practice. A common feature of the modern birth space is the bed. Knowledge about how the use of the bed shapes clinicians' perceptions and attitudes is limited. Aim: The aim of this paper is to describe midwives' perceptions of the birth bed. Method: Qualitative descriptive design. Fourteen midwives from one Queensland maternity unit participated in digitally recorded and transcribed interviews. Thematic analysis was used to analyse the data set. Findings: Four themes were identified. The first, described beliefs that using the bed formed part of women's childbirth expectations. A second theme, captured midwives' perceptions that the bed was also an object required to safely undertake their work. The third theme described how others commonly worked to ensure the woman stayed off the bed. Lastly, there was evidence that whilst wanting to avoid the use of the bed, some were reluctant, fearing potential reprimand. Conclusion: The themes highlight differences in how the midwives conceptualised the use of a bed within a birth space. While some avoided the use of the bed altogether others would only conceive of women moving off the bed if everything was 'normal'. How the bed was culturally constructed appeared to dictate clinical practice. Reflecting on the meaning of an object, such as the bed, is important if clinicians are to fully understand how the birth environment influences their practice and thus women's experiences of labour and birth.

Universal access to affordable medicines, which are safe, efficacious and of high quality, and which are appropriately used, depends on national legislation that is in turn constrained by a range of international agreements. This regulatory configuration also affects the profitability of the pharmaceutical industry, domestic and international. Tensions and contradictions between industry profitability and public health objectives relate to access, innovation and regulation.

Despite recent advances in harnessing cortical motor-related activity to control computer cursors and robotic devices, the ability to decode and execute different grasping patterns remains a major obstacle. Here we demonstrate a simple Bayesian decoder for real-time classification of grip type and wrist orientation in macaque monkeys that uses higher-order planning signals from anterior intraparietal cortex (AIP) and ventral premotor cortex (area F5). Real-time decoding was based on multiunit signals, which had similar tuning properties to cells in previous single-unit recording studies. Maximum decoding accuracy for two grasp types (power and precision grip) and five wrist orientations was 63% (chance level, 10%). Analysis of decoder performance showed that grip type decoding was highly accurate (90.6%), with most errors occurring during orientation classification. In a subsequent off-line analysis, we found small but significant performance improvements (mean, 6.25 percentage points) when using an optimized spike-sorting method (superparamagnetic clustering). Furthermore, we observed significant differences in the contributions of F5 and AIP for grasp decoding, with F5 being better suited for classification of the grip type and AIP contributing more toward decoding of object orientation. However, optimum decoding performance was maximal when using neural activity simultaneously from both areas. Overall, these results highlight quantitative differences in the functional representation of grasp movements in AIP and F5 and represent a first step toward using these signals for developing functional neural interfaces for hand grasping.