Reversible Protonated Resting State of the Nitrogenase Active Site

Protonated states of the nitrogenase active site are mechanistically significant since substrate reduction is invariably accompanied by proton uptake. We report the low pH characterization by X-ray crystallography and EPR spectroscopy of the nitrogenase molybdenum iron (MoFe) proteins from two phylogenetically distinct nitrogenases (Azotobacter vinelandii, Av, and Clostridium pasteurianum, Cp) at pHs between 4.5 and 8. X-ray data at pHs of 4.5–6 reveal the repositioning of side chains along one side of the FeMo-cofactor, and the corresponding EPR data shows a new S = 3/2 spin system with spectral features similar to a state previously observed during catalytic turnover. The structural changes suggest that FeMo-cofactor belt sulfurs S3A or S5A are potential protonation sites. Notably, the observed structural and electronic low pH changes are correlated and reversible. The detailed structural rearrangements differ between the two MoFe proteins, which may reflect differences in potential protonation sites at the active site among nitrogenase species. These observations emphasize the benefits of investigating multiple nitrogenase species. Our experimental data suggest that reversible protonation of the resting state is likely occurring, and we term this state “E_0H+”, following the Lowe–Thorneley naming scheme

Evaluating the impacts on health outcomes of Welsh Government funded schemes designed to improve the energy efficiency of the homes of low income households: A comparison of individual level and area based schemes.

Introduction Living in a cold and/or damp house can damage health. To reduce fuel poverty in Wales, the Welsh Government developed domestic energy efficiency schemes - an individual-level scheme, Warm Homes Nest and an area-based scheme, Warm Homes Arbed. Both schemes provide improvements to those most likely affected by fuel poverty. Objectives and Approach Overall aim: to evaluate the health impacts of Welsh Government funded schemes designed to reduce fuel poverty. Presented objective: to investigate the relative impact of the individual-level and area-based schemes on the health of recipients. A longitudinal dataset was created using the anonymised residence that received improvements linked to residents’ health measures (hospital admissions, GP prescriptions and clinical diagnoses) using routine health records held in the SAIL Databank at Swansea University. We used difference-in-difference (DID) estimations to compare any changes in recipient health before and after intervention with any concurrent change in health in those yet to receive the intervention. Results An analysis of the Warm Homes Nest Scheme, published in 2017 and presented at the IPDLN 2017 conference found a positive impact of the scheme on the health of recipients. This presentation will describe the further analysis (concluding shortly) comparing the area-based Arbed scheme with both the recipients of the individual-level Nest scheme and groups in comparable need that had not yet received the intervention. We will present results focussing on the relative impacts of the two schemes on cardiovascular, respiratory and general health. Conclusion/Implications Providing home energy efficiency interventions has the potential to benefit population health; however, there is a scarcity of evidence comparing different methods of implementing schemes. Our findings will inform more effectively-focussed home energy efficiency schemes and potentially thus improve the health of people living in Wales

A policy impact case study using real world data from Welsh government fuel poverty schemes to inform scheme design

Objectives To reduce fuel poverty in Wales: the Welsh Government developed schemes to provide energy efficiency improvements to lower income households. To inform scheme design: investigate health impacts by linking scheme data to health records. Presented objective: to demonstrate how research findings using real world data can impact policy focus. Approach The research was conducted by an independent researcher at Swansea University who co-produced research questions with the Welsh Government Fuel Poverty Policy Team. A longitudinal dataset was created linking anonymised ‘Warm Homes: Nest’ improvements data to residents’ routine health records in the SAIL Databank at Swansea University. We examined recipient health before and after intervention compared with controls. A high-level policy briefing and research report were published in the Welsh Government Social Research – Analysis for Policy series. Findings were used to design and pilot new eligibility criteria to capture low-income individuals with a respiratory, circulatory or mental health condition. Results This presentation will describe the policy impact pathway from initial discussions with policymakers to real world change, including: • securing ESRC funding for a Knowledge Transfer Fellowship, which included a 2013 data linking demonstration project… • …which allowed funding to be secured for a 2015-18 research project on the impact of improvements on recipient health… • …which published emerging findings in 2016… • …and substantive findings in 2017, showing a significant positive impact of improvements on recipient health… • …which policymakers used to design a pilot to test ways to widen eligibility criteria to include individuals on a low income with a respiratory, circulatory or mental health condition… • …which led to scheme criteria being widened in 2019. By 2021, 25% of recipients entered the scheme via the ‘health route’. Conclusion By delivering research findings generated using linked real world data, and focused on questions co-produced with policymakers, researchers can successfully impact the design and implementation of government policy, thereby improving the lives of people in the real world - in this case, the health of the citizens of Wales

Evaluating the impacts on health outcomes ofWelsh Government funded schemes designed to improve the energy efficiency of the homes of low income households: A comparison of individual level and area based schemes.

Background To reduce fuel poverty and its adverse health effects in Wales the Welsh Government developed programmes to improve the energy efficiency of homes. This includes the fuel poverty scheme: ‘Warm Homes Nest‘. The scheme was available to low income and vulnerable households in Wales from 2011 to 2015, and provided energy efficiency measures e.g. insulation and heating upgrades such as a more efficient boiler, aimed to maintain warmer homes. Objectives The overall aim was to evaluate the health impacts of Welsh Government funded schemes designed to reduce fuel poverty through the use of existing data linked to the routine health records held in the SAIL Databank at Swansea University. Method We created a longitudinal dataset of individuals living in residential dwellings in receipt of home energy efficiency improvements, then linked to their health records to create a summary of their health utilization measures. We used difference-in-difference (DID) estimations to compare any changes in recipient health before and after intervention against any concurrent change in health in those yet to receive the intervention. Findings We have built upon our previous work presented at the ADRN 2017 conference where we reported a positive impact of the Nest scheme on the respiratory health of recipients. We will show a significant impact on respiratory conditions leading to a change to the eligibility criteria for the successor scheme. We will discuss our ongoing work analysing the impacts of the Nest scheme on mental health outcomes. This will include the findings from the literature search demonstrating the need for more evidence using objective outcome measures, and on selecting and utilizing validated codes developed for administrative data to investigate any changes in common mental health issues such as depression and anxiety. Conclusions Providing home energy efficiency interventions has the potential to benefit population health. Our findings will inform more effectively-focussed home energy efficiency schemes and potentially thus improve the health of people living in Wales

Multiple and multi-dimensional transitions from trainee to trained doctor: A qualitative longitudinal study in the UK

Objectives To explore trainee doctors’ experiences of the transition to trained doctor, we answer three questions: (1) What multiple and multidimensional transitions (MMTs) are experienced as participants move from trainee to trained doctor? (2) What facilitates and hinders doctors’ successful transition experiences? (3) What is the impact of MMTs on trained doctors? Design: A qualitative longitudinal study underpinned by MMT theory. Setting: Four training areas (health boards) in the UK. Participants: 20 doctors, 19 higher-stage trainees within 6 months of completing their postgraduate training and 1 staff grade, associate specialist or specialty doctor, were recruited to the 9-month longitudinal audio-diary (LAD) study. All completed an entrance interview, 18 completed LADs and 18 completed exit interviews. Methods: Data were analysed cross-sectionally and longitudinally using thematic Framework Analysis. Results: Participants experienced a multiplicity of expected and unexpected, positive and negative work-related transitions (eg, new roles) and home-related transitions (eg, moving home) during their trainee–trained doctor transition. Factors facilitating or inhibiting successful transitions were identified at various levels: individual (eg, living arrangements), interpersonal (eg, presence of supportive relationships), systemic (eg, mentoring opportunities) and macro (eg, the curriculum provided by Medical Royal Colleges). Various impacts of transitions were also identified at each of these four levels: individual (eg, stress), interpersonal (eg, trainees’ children spending more time in childcare), systemic (eg, spending less time with patients) and macro (eg, delayed start in trainees’ new roles). Conclusions: Priority should be given to developing supportive relationships (both formal and informal) to help trainees transition into their trained doctor roles, as well as providing more opportunities for learning. Further longitudinal qualitative research is now needed with a longer study duration to explore transition journeys for several years into the trained doctor role

AD|ARC (Administrative Data | Agricultural Research Collection): Linking individual, household and farm business data for agricultural research – Challenges of linking agricultural datasets with individual-level records

Objectives To create an anonymised research-ready data resource of farm households in the UK to generate evidence to support policy development, implementation and evaluation; improve understanding of farm family socio-economic characteristics; and assist stakeholders interested in understanding the health and well-being, resilience and prosperity and spatial properties of farming communities. Methods The ADARC research-ready data resource is being created in each nation of the UK. Each core dataset links agricultural datasets with individual- and household-level population data from the Census 2011. The farm business data is drawn from a number of sources (the Inter Departmental Business Register, EU Farm Structure Survey 2010 and Rural Payments data), which presented many data preparation challenges when linking to the Census of Population. Each core dataset will be linked to the health and education data available for that nation. Where possible, the ADARC datasets have been harmonised to allow federated querying across the UK. Results The ADARC core datasets are complete in Wales and near completion in England and Scotland. Work is also well advanced in Northern Ireland. To the best of our knowledge, these are the first datasets linking agricultural data to individual- and household-level data at a population level. We will report the challenges experienced in linking farm business data with data at the household and individual level. This will include a description of the data preparation steps, the challenges encountered and solutions utilised at each stage of building this complex dataset from numerous, very different ‘parent’ datasets. The structure and content of the core datasets will be presented as well as the potential benefits to researchers investigating the individual, household and community dimensions of agricultural research. Conclusion Agriculture is currently facing a range of challenges with little known about the impact on farmers and farming households. ADARC introduces a new, powerful and versatile resource that will help inform debate and potentially lead to better outcomes on a range of issues relevant to farmers and farming communities

Establishment of a National Homelessness Prevention Programme dataset to enable an anonymised longitudinal dynamic cohort based study

Introduction Welsh Government invests over £120m annually in housing related support to help prevent and tackle homelessness under the ‘Supporting People Programme’. A 2016 data-linkage Feasibility Study indicated health-service utilisation reductions post-intervention, and led to a four year project to create a national, all-Wales dataset to provide robust statistical results. Objectives and Approach Establish data sharing agreements, acquire and import anonymised individual-level data into the SAIL Databank. Create a research ready dataset, designed to permit annual administrative data updates to form dynamic cohort and control groups. Create several control group methods: 1) Internal Programme Data; 2) Matched controls; 3) Healthcare-Utilisation Patterns; 4) External Data Sources. Link to routine health data, obtain and link to other public service data to gain a deeper understanding of the Programme; how it affects use of other public services, and whether it helps people live independently. Complete statistical analysis using a Generalised Linear Mixed Modelling approach. Results Data sharing agreements, data acquisition and standardisation complete for nineteen of twenty-two Unitary Authorities in Wales. Temporal coverage varies by Unitary Authority (2003-2017). 2016 data measures: match rates >85%; 57% female; lead reason for support (top 5) : ‘General’ 20%, ‘Mental Health’ 15%, ‘Older People’ 14%, ‘Domestic Abuse’ 9%, ‘Young People’ 7%. Various control group methods employed: 1) Internal ‘Programme’ Data – no support taken up; 2) Matched controls; 3) Healthcare-Utilisation Patterns – rejected due to sparse outcome data; 4) External Data Sources being further explored. Health data-linkage (emergency admissions, emergency department attendance and primary care events) complete. Ongoing discussions to obtain sample social care, and police call data during 2018. Statistical analysis underway with results planned to be published during the summer of 2018. Conclusion/Implications Despite many challenges, creation of a national linked dataset for people at risk of homelessness is possible with collaborative working between central government, academic and local government bodies. This ‘Administrative Data Research Centre Wales’ project has created a rich research resource enabling statistical analysis to answer research questions around homelessness

Fe K\alpha emission from photoionized slabs: the impact of the iron abundance

Iron K\alpha emission from photoionized and optically thick material is observed in a variety of astrophysical environments including X-ray binaries, active galactic nuclei, and possibly gamma-ray bursts. This paper presents calculations showing how the equivalent width (EW) of the Fe K line depends on the iron abundance of the illuminated gas and its ionization state -- two variables subject to significant cosmic scatter. Reflection spectra from a constant density slab which is illuminated with a power-law spectrum with photon-index \Gamma are computed using the code of Ross & Fabian. When the Fe K EW is measured from the reflection spectra alone, we find that it can reach values greater than 6 keV if the Fe abundance is about 10 times solar and the illuminated gas is neutral. EWs of about 1 keV are obtained when the gas is ionized. In contrast, when the EW is measured from the incident+reflected spectrum, the largest EWs are ~800 keV and are found when the gas is ionized. When \Gamma is increased, the Fe K line generally weakens, but significant emission can persist to larger ionization parameters. The iron abundance has its greatest impact on the EW when it is less than 5 times solar. When the abundance is further increased, the line strengthens only marginally. Therefore, we conclude that Fe K lines with EWs much greater than 800 eV are unlikely to be produced by gas with a supersolar Fe abundance. These results should be useful in interpreting Fe K emission whenever it arises from optically thick fluorescence.Comment: 5 pages, 5 figures, accepted by MNRAS Letter

First Constraints on Iron Abundance versus Reflection Fraction from the Seyfert~1 Galaxy MCG--6-30-15

We report on a joint ASCA and RXTE observation spanning an $\sim$ 400~ks time interval of the bright Seyfert~1 galaxy MCG--6-30-15. The data clearly confirm the presence of a broad skewed iron line ($W_{K\alpha} \sim$ 266 eV) and Compton reflection continuum at higher energies reported in our previous paper. We also investigate whether the gravitational and Doppler effects that affect the iron line may also be manifest in the reflected continuum. The uniqueness of this data set is underlined by the extremely good statistics that we obtain from the approximately four million photons that make up the 2-20 keV RXTE PCA spectrum alone. This, coupled with the high energy coverage of HEXTE and the spectral resolution of ASCA in the iron line regime has allowed us to constrain the relationship between abundance and reflection fraction for the first time at the 99 per cent confidence level. The reflection fraction is entirely consistent with a flat disk, i.e. the cold material subtends $\rm 2 \pi$ sr at the source, to an accuracy of 20 per cent. Monte Carlo simulations show that the observed strong iron line intensity is explained by an overabundance of iron by a factor of $\sim$ 2 and an underabundance of the lower-Z elements by a similar factor. By considering non-standard abundances, a clear and consistent picture can be made in which both the iron line and reflection continuum come from the same material such as e.g. an accretion disk.Comment: 8 pages, 8 figures, accepted for publication MNRAS 7/9