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We present new JWST NIRSpec integral field spectroscopy (IFS) data for the luminous infrared galaxy NGC 7469, a nearby (70.6 Mpc) active galaxy with a Seyfert 1.5 nucleus that drives a highly ionized gas outflow and a prominent nuclear star-forming ring. Using the superb sensitivity and high spatial resolution of the JWST instrument NIRSpec IFS, we investigate the role of the Seyfert nucleus in the excitation and dynamics of the circumnuclear gas. Our analysis focuses on the [Fe ii ], H _2 , and hydrogen recombination lines that trace the radiation/shocked-excited molecular and ionized interstellar medium around the active galactic nucleus (AGN). We investigate gas excitation through H _2 /Br γ and [Fe ii ]/Pa β emission line ratios and find that photoionization by the AGN dominates within the central 300 pc of the galaxy except in a small region that shows signatures of shock-heated gas; these shock-heated regions are likely associated with a compact radio jet. In addition, the velocity field and velocity dispersion maps reveal complex gas kinematics. Rotation is the dominant feature, but we also identify noncircular motions consistent with gas inflows as traced by the velocity residuals and the spiral pattern in the Pa α velocity dispersion map. The inflow is 2 orders of magnitude higher than the AGN accretion rate. The compact nuclear radio jet has enough power to drive the highly ionized outflow. This scenario suggests that the inflow and outflow are in a self-regulating feeding–feedback process, with a contribution from the radio jet helping to drive the outflow.

We present James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec) integral field spectroscopy of the nearby luminous infrared galaxy NGC 7469. We take advantage of the high spatial/spectral resolution and wavelength coverage of JWST/NIRSpec to study the 3.3 μ m neutral polycyclic aromatic hydrocarbon (PAH) grain emission on ∼200 pc scales. A clear change in the average grain properties between the star-forming ring and the central AGN is found. Regions in the vicinity of the AGN, with [Ne iii ]/[Ne ii ] > 0.25, tend to have larger grain sizes and lower aliphatic-to-aromatic (3.4/3.3) ratios, indicating that smaller grains are preferentially removed by photodestruction in the vicinity of the AGN. PAH emission at the nucleus is weak and shows a low 11.3/3.3 PAH ratio. We find an overall suppression of the total PAH emission relative to the ionized gas in the central 1 kpc region of the AGN in NGC 7469 compared to what has been observed with Spitzer on 3 kpc scales. However, the fractional 3.3 μ m–to–total PAH power is enhanced in the starburst ring, possibly due to a variety of physical effects on subkiloparsec scales, including recurrent fluorescence of small grains or multiple photon absorption by large grains. Finally, the IFU data show that while the 3.3 μ m PAH-derived star formation rate (SFR) in the ring is 27% higher than that inferred from the [Ne ii ] and [Ne iii ] emission lines, the integrated SFR derived from the 3.3 μ m feature would be underestimated by a factor of 2 due to the deficit of PAHs around the AGN, as might occur if a composite system like NGC 7469 were to be observed at high redshift.

The nearby, luminous infrared galaxy NGC 7469 hosts a Seyfert nucleus with a circumnuclear star-forming ring and is thus the ideal local laboratory for investigating the starburst–AGN (active galactic nucleus) connection in detail. We present integral-field observations of the central 1.3 kpc region in NGC 7469 obtained with the JWST Mid-InfraRed Instrument. Molecular and ionized gas distributions and kinematics at a resolution of ∼100 pc over the 4.9–7.6 μ m region are examined to study the gas dynamics influenced by the central AGN. The low-ionization [Fe ii ] λ 5.34 μ m and [Ar ii ] λ 6.99 μ m lines are bright on the nucleus and in the starburst ring, as opposed to H _2 S(5) λ 6.91 μ m, which is strongly peaked at the center and surrounding ISM. The high-ionization [Mg v ] line is resolved and shows a broad, blueshifted component associated with the outflow. It has a nearly face-on geometry that is strongly peaked on the nucleus, where it reaches a maximum velocity of −650 km s ^−1 , and extends about 400 pc to the east. Regions of enhanced velocity dispersion in H _2 and [Fe ii ] ∼ 180 pc from the AGN that also show high L (H _2 )/ L (PAH) and L ([Fe ii ])/ L (Pf α ) ratios to the W and N of the nucleus pinpoint regions where the ionized outflow is depositing energy, via shocks, into the dense interstellar medium between the nucleus and the starburst ring. These resolved mid-infrared observations of the nuclear gas dynamics demonstrate the power of JWST and its high-sensitivity integral-field spectroscopic capability to resolve feedback processes around supermassive black holes in the dusty cores of nearby luminous infrared galaxies.

We present James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) integral-field spectroscopy of the nearby merging, luminous infrared galaxy, NGC 7469. This galaxy hosts a Seyfert type-1.5 nucleus, a highly ionized outflow, and a bright, circumnuclear star-forming ring, making it an ideal target to study active galactic nucleus (AGN) feedback in the local universe. We take advantage of the high spatial/spectral resolution of JWST/MIRI to isolate the star-forming regions surrounding the central active nucleus and study the properties of the dust and warm molecular gas on ∼100 pc scales. The starburst ring exhibits prominent polycyclic aromatic hydrocarbon (PAH) emission, with grain sizes and ionization states varying by only ∼30%, and a total star formation rate of 10–30 M _⊙ yr ^−1 derived from fine structure and recombination emission lines. Using pure rotational lines of H _2 we detect 1.2 × 10 ^7 M _⊙ of warm molecular gas at a temperature higher than 200 K in the ring. All PAH bands get significantly weaker toward the central source, where larger and possibly more ionized grains dominate the emission, likely the result of the ionizing radiation and/or the fast wind emerging from the AGN. The small grains and warm molecular gas in the bright regions of the ring however display properties consistent with normal star-forming regions. These observations highlight the power of JWST to probe the inner regions of dusty, rapidly evolving galaxies for signatures of feedback and inform models that seek to explain the coevolution of supermassive black holes and their hosts.

The economic evaluation which supports Health Technology Assessment (HTA) should inform policy makers of the value to society conferred by a given allocation of resources. However, neither the theory nor practise of economic evaluation satisfactorily reflect social values. Both are primarily concerned with efficiency, commonly conceptualised as the maximisation of utility or quality adjusted life years (QALYs). The focus is upon the service and the benefits obtained from it. This has resulted in an evaluation methodology which discriminates against groups and treatments which the population would like to prioritise. This includes high cost treatments for patients with rare diseases. In contrast with prevailing methods, there is increasing evidence that the public would prefer a fairness-focused framework in which the service was removed from centre stage and replaced by the patient. However methods for achieving fairness are ad hoc and under-developed. The article initially reviews the theory of economic evaluation and argues that its focus upon individual utility and efficiency as defined by the theory omits potentially important social values. Some empirical evidence relating to population values is presented and four studies by the first author are reviewed. These indicate that when people adopt the social perspective of a citizen they have a preference for sharing the health budget in a way which does not exclude patients who require services that are not cost effective, such as orphan medicinal products (OMP’s) and treatments for patients with ultra-rare diseases (URD’s).

Table of contents O1 The European Social Preferences Measurement (ESPM) study project: social cost value analysis, budget impact, commercial life cycle revenue management, and the economics of biopharmaceutical Research & Development (R&D) Michael Schlander, Søren Holm, Erik Nord, Jeff Richardson, Silvio Garattini, Peter Kolominsky-Rabas, Deborah Marshall, Ulf Persson, Maarten Postma, Steven Simoens, Oriol de Solà Morales, Keith Tolley, Mondher Toumi, Harry Telser O2 Newborn Screening: the potential and the challenges James R Bonham O3 Untreatable disease outcomes - how would we measure them? Helmut Hintner, Anja Diem, Martin Laimer O4 Taking Integrated Care Forward: Experiences from Canada to inspire service provision for people living with rare disease in Europe Réjean Hébert O5 Listening to the patient’s voice: social media listening for safety and benefits in rare diseases Nabarun Dasgupta, Carrie E. Pierce, Melissa Jordan O6 Via Opta: Mobile apps making visually impaired patients’ lives easier Barbara Bori, Mohanad Fors, Emilie Prazakova O7 A report of the IRDiRC “Small Population Clinical Trial” Task Force Simon Day O8 HAE patient identification and diagnosis: An innovative, ‘game changing’ collaboration Thomas J. Croce Jr. O9 Co-creating with the community: primary packaging & administration for people with haemophilia Jonas Fransson, Philip Wood O10 Go with Gaucher, taking forward the next generation. How to involve young people to create a new generation of patient advocates Anne-Grethe Lauridsen, Joanne Higgs, Vesna Stojmirova Aleksovska P1 ODAK – Orphan Drug for Acanthamoeba Keratitis Christina Olsen, Ritchie Head, Antonio Asero, Vincenzo Papa, Christa van Kan, Loic Favennec, Silvana Venturella, Michela Salvador, Alan Krol P5 Rare Navigators help people living with rare diseases to manage the social – and healthcare systems Stephanie J. Nielsen, Birthe B. Holm P6 The eAcademy for Tay-Sachs & Sandhoff disease app Daniel Lewi, Patricia Durão P10 The role of a patient organisation in driving the research agenda in a rare disease Heather Band, Andrea West P13 Expertise for rare diseases mapped Marinda J.A. Hammann, Marije C. Effing-Boele, Hanka K. Dekker P14 The hidden costs of rare diseases: a feasibility study Amy Hunter, Amy Simpson P15 FDA’s new natural history grant program: support to build a solid foundation for development of products for rare diseases Gumei Liu, Katherine Needleman, Debra Lewis, Gayatri Rao P17 Understanding the wider impact of adrenal insufficiency: patient organisation involvement in the TAIN project Amy Simpson, Amy Hunter, Martin J Whitaker P20 Bridging the gaps between medical and social care for people living with a rare disease Raquel Castro

Patients with a permanent impairment may be unable to reach full health. Consequently health services which cure illnesses which are unrelated to the impairment may increase health less than services for patients with no impairment. While it has been argued that this should not lead to discrimination against impaired patients there is little evidence to determine whether this equity-efficiency trade-off is consistent with social values.To measure the effect of permanent impairment upon the social valuation of services for unrelated illnesses.Social valuations of services for illnesses associated with mobility, depression or pain were assessed and compared for patients with and without a permanent impairment using the Relative Social Willingness to Pay (RS-WTP) instrument. The maximum valuation of services for impaired patients was also compared with the maximum utility which could be gained when utility was measured using three multi attribute utility instruments.Curing the illness of impaired patients was valued 8-11 percent less than the cure of patients with no impairment. Discrimination decreased as the severity of the illness increased. Valuation of health states using the utility instruments implied significantly greater discrimination than the social valuations using the RS-WTP instrument.Health services are valued less highly when a patient's health potential is impaired. However discrimination is significantly less than would occur if the value of the services were limited to the value of the health state causing the impairment. The argument for disregarding a patient's limited health potential when resources are allocated therefore receives some support from social valuations but the case for completely equal treatment depends upon additional ethical arguments.

Abstract Objective : To provide Australian health‐related quality of life (HRQoL) population norms, based on utility scores from the Assessment of Quality of Life (AQoL) measure, a participant‐reported outcomes (PRO) instrument. Methods: The data were from the 2007 National Survey of Mental Health and Wellbeing. AQoL scores were analysed by age cohorts, gender, other demographic characteristics, and mental and physical health variables. Results: The AQoL utility score mean was 0.81 (95%CI 0.81–0.82), and 47% obtained scores indicating a very high HRQoL (>0.90). HRQoL gently declined by age group, with older adults’ scores indicating lower HRQoL. Based on effect sizes (ESs), there were small losses in HRQoL associated with other demographic variables (e.g. by lack of labour force participation, ESmedian: 0.27). Those with current mental health syndromes reported moderate losses in HRQoL (ESmedian: 0.64), while those with physical health conditions generally also reported moderate losses in HRQoL (ESmedian: 0.41). Conclusions: This study has provided contemporary Australian population norms for HRQoL that may be used by researchers as indicators allowing interpretation and estimation of population health (e.g. estimation of the burden of disease), cross comparison between studies, the identification of health inequalities, and to provide benchmarks for health care interventions.

OBJECTIVES: The objective of this study was to describe and measure the loss of health related quality of life (HRQoL) associated with obesity using two generic instruments. The first of these, the SF-36, is the most widely used and validated HRQoL instrument worldwide. However, it does not provide utility weights and cannot be used to measure quality adjusted life years (QALYs), an increasingly common unit for comparing the effect of health states in economic evaluation studies. The second, the AQoL-8D, is a multi-attribute utility (MAU) instrument which was developed to increase sensitivity of previous MAU instruments to psycho-social dimensions of a health state and to allow the calculation of QALYs. Since the two instruments differ, an important additional objective of the study was to determine the validity of the AQoL-8D as judged by the SF-36, and therefore the confidence which might be placed upon its use in the context of obesity. METHODS: Data were obtained from patients waiting for bariatric surgery who had completed both the SF-36 and AQoL-8D quality of life instruments and a general questionnaire including height, weight, demographic and socio-economic information. For comparative purposes, scores were standardized using results from a representative sample of the general population. The content validity of the AQoL-8D was assessed by comparing it with the dimension scores from the SF-36 and the summary component (physical and mental) scores. Overall scores from the SF-36 and AQoL-8D instruments were regressed upon patient BMI and the results from the AQoL-8D used to estimate the effect of overweight and obesity upon utility and lost QALYs. RESULTS: The comparison of the instruments indicated that the AQoL-8D has good convergent, concurrent and content validity. Using both instruments, obesity was significantly associated with lower scores for 14 of their 16 dimensions. AQoL-8D, in particular, identified a significant decrease in psychological and social health with happiness, self-worth, coping and mental health, all being poorer than in the control group. Regression results implied that a change in BMI from 30 to 50 decreases utility by 0.12 or by 13.8 percent of the average utility for a 25-35 year old. CONCLUSION: AQoL-8D is a valid measure of utility in the context of obesity. Its inclusion of psycho-social effects significantly increases the measured adverse effects of obesity.

BackgroundEvaluations of the impact of interventions for resource allocation purposes commonly focus on health status. There is, however, also concern about broader impacts on wellbeing and, increasingly, on a person's capability. This study aims to compare the impact on health status and capability of seven major health conditions, and highlight differences in treatment priorities when outcomes are measured by capability as opposed to health status.MethodsThe study was a cross-sectional four country survey (n = 6650) of eight population groups: seven disease groups with: arthritis, asthma, cancer, depression, diabetes, hearing loss, and heart disease and one health population 'comparator' group. Two simple self-complete questionnaires were used to measure health status (EQ-5D-5L) and capability (ICECAP-A). Individuals were classified by illness severity using condition-specific questionnaires. Effect sizes were used to estimate: (i) the difference in health status and capability for those with conditions, relative to a healthy population; and (ii) the impact of the severity of the condition on health status and capability within each disease group.Findings5248 individuals were included in the analysis. Individuals with depression have the greatest mean reduction in both health (effect size, 1.26) and capability (1.22) compared to the healthy population. The effect sizes for capability for depression are much greater than for all other conditions, which is not the case for health. For example, the arthritis group effect size for health (1.24) is also high and similar to that of depression, whereas for the same arthritis group, the effect size for capability is much lower than that for depression (0.55). In terms of severity within disease groups, individuals categorised as 'mild' have similar capability levels to the healthy population (effect sizes ConclusionSignificant differences exist in the relative effect sizes across diseases when measured by health status and capability. In terms of treating morbidity, a shift in focus from health gain to capability gain would increase funding priorities for patients with depression specifically and severe illnesses more generally.

Using Spitzer observations of classical Cepheids we have measured the true average distance modulus of the Small Magellanic Cloud (SMC) to be mag (corresponding to kpc), which is 0.48 ± 0.01 mag more distant than the LMC. This is in agreement with previous results from Cepheid observations, as well as with measurements from other indicators such as RR Lyrae stars and the tip of the red giant branch. Utilizing the properties of the mid-infrared Leavitt Law we measured precise distances to individual Cepheids in the SMC, and have confirmed that the galaxy is tilted and elongated such that its eastern side is up to 20 kpc closer than its western side. This is in agreement with the results from red clump stars and dynamical simulations of the Magellanic Clouds and Stream. [ABSTRACT FROM AUTHOR]