The social value of a QALY : raising the bar or barring the raise?

Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England, there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were released during a time of considerable debate about the NICE threshold, and authors with differing perspectives have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for those who conducted the research to contribute to the debate as to its implications for NICE. Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’ answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the other that greater weight could be given to QALYs gained by some groups. Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be moved up for some types of QALY and down for others. While many members of the public appear to be open to the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have any secure evidence base for introducing such a system

Enhanced Secretion of Amylase from Exocrine Pancreas of Connexin32-deficient Mice

To determine whether junctional communication between pancreatic acinar cells contributes to their secretory function in vivo, we have compared wild-type mice, which express the gap junctional proteins connexin32 (Cx32) and connexin26, to mice deficient for the Cx32 gene. Pancreatic acinar cells from Cx32 (−/−) mice failed to express Cx32 as evidenced by reverse transcription–PCR and immunolabeling and showed a marked reduction (4.8- and 25-fold, respectively) in the number and size of gap junctions. Dye transfer studies showed that the extent of intercellular communication was inhibited in Cx32 (−/−) acini. However, electrical coupling was detected by dual patch clamp recording in Cx32 (−/−) acinar cell pairs. Although wild-type and Cx32 (−/−) acini were similarly stimulated to release amylase by carbamylcholine, Cx32 (−/−) acini showed a twofold increase of their basal secretion. This effect was caused by an increase in the proportion of secreting acini, as detected with a reverse hemolytic plaque assay. Blood measurements further revealed that Cx32 (−/−) mice had elevated basal levels of circulating amylase. The results, which demonstrate an inverse relationship between the extent of acinar cell coupling and basal amylase secretion in vivo, support the view that the physiological recruitment of secretory acinar cells is regulated by gap junction mediated intercellular communication

Can i have a second child? dilemmas of mothers of children with pervasive developmental disorder: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Pervasive developmental disorder (PDD) has an uncertain etiology, no method of treatment, and results in communication deficiencies and other behavioral problems. As the reported recurrence risk is 5%-10% and there are no methods of either prevention or prenatal testing, mothers of PDD children may face unique challenges when contemplating second pregnancies. The purpose of this study was to explore the mothers' lived experiences of second child-related decision-making after the birth of a child with PDD.</p> <p>Methods</p> <p>The participants for this study were restricted to mothers living within the greater Tokyo metropolitan area who had given birth to a first child with PDD within the past 18 years. The ten participants were encouraged to describe their experiences of second-child related decision-making after the birth of a child with PDD on the basis of semi-structured interviews. Data analysis was performed by using Interpretive Phenomenological Analysis (IPA), which is concerned with understanding what the participant thinks or believes about the topic under discussion.</p> <p>Results</p> <p>We identified two superordinate themes. The first was balancing hopes and fears, in which hope was the potential joy to be gained by the birth of a new child without PDD and fears were characterized as uncertainty of PDD and perception of recurrence risk, burden on later-born children, and negative effects on a child with PDD.</p> <p>The second superordinate theme was assessing the manageability of the situation, which was affected by factors as diverse as severity of PDD, relationship between mother and father, and social support and acceptance for PDD. Our 10 participants suffered from extreme psychological conflict, and lack of social support and acceptance for PDD created numerous practical difficulties in having second children.</p> <p>Conclusions</p> <p>Our participants faced various difficulties when considering second pregnancies after the birth of children with PDD in the Japanese society. As lack of social support and acceptance for PDD also played a large role in second child-related decision-making, creating a social environment that more fully accepts those disabled and providing flexible support systems for families of children with PDD are crucial.</p

Heterogeneity in drinking practices in England and Wales and its association with violent behaviour: a latent class analysis

Background: Crude single-item consumption metrics, such as ‘binge drinking’ measures, mask the complexity and heterogeneity in young people’s drinking; thus limiting our understanding of young people’s drinking patterns as well as how alcohol drinking is associated with violent outcomes. Objectives: The current study employed a range of consumption and contextual indicators to explore heterogeneity in young people’s (16-29 years) drinking practices, giving due consideration to their social nature. It also assessed to what extent heterogeneity in drinking practices was associated with violent outcomes. Methods: Employing data from the 2006 Offending Crime and Justice Survey, three measures of alcohol consumption and nine drinking context indicators were utilised within latent class analysis to create typologies of drinking practices amongst current drinkers in England and Wales (n=2,711) and examine their association with violent outcomes. The validity of the typologies was also assessed on age, sex and socio-economic status. Results: Three discernible drinking profiles were identified: ‘regular social drinkers’ (48%), ‘regular pub binge drinkers’ (32%), and ‘moderate drinkers’ (20%). The ‘regular pub binge drinkers’ were found to be more than twice as likely to commit an assault offence (odds ratio = 2.8 95% CI [1.3, 6.2]) when compared to ‘moderate drinkers’. Interaction analyses demonstrated a stronger risk of violence among ‘regular social drinkers’ of low socio-economic status. Conclusions: Interventions aimed at reducing alcohol-related violence ought to give due consideration to the social context of drinking, the levels of consumption, as well as the socio-economic characteristics of the drinker

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5– 20 deg2 requires at least three detectors of sensitivity within a factor of ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone

Directional Limits on Persistent Gravitational Waves from Advanced LIGO’s First Observing Run

We employ gravitational-wave radiometry to map the stochastic gravitational wave background expected from a variety of contributing mechanisms and test the assumption of isotropy using data from the Advanced Laser Interferometer Gravitational Wave Observatory’s (aLIGO) first observing run. We also search for persistent gravitational waves from point sources with only minimal assumptions over the 20–1726 Hz frequency band. Finding no evidence of gravitational waves from either point sources or a stochastic background, we set limits at 90% confidence. For broadband point sources, we report upper limits on the gravitational wave energy flux per unit frequency in the range Fα;ΘðfÞ < ð0.1–56Þ × 10−8 erg cm−2 s−1 Hz−1ðf=25 HzÞα−1 depending on the sky location Θ and the spectral power index α. For extended sources, we report upper limits on the fractional gravitational wave energy density required to close the Universe of Ωðf; ΘÞ < ð0.39–7.6Þ × 10−8 sr−1ðf=25 HzÞα depending on Θ and α. Directed searches for narrowband gravitational waves from astrophysically interesting objects (Scorpius X-1, Supernova 1987 A, and the Galactic Center) yield median frequency-dependent limits on strain amplitude of h0 < ð6.7; 5.5; and 7.0Þ × 10−25, respectively, at the most sensitive detector frequencies between 130–175 Hz. This represents a mean improvement of a factor of 2 across the band compared to previous searches of this kind for these sky locations, considering the different quantities of strain constrained in each case

GWTC-1: A Gravitational-Wave Transient Catalog of Compact Binary Mergers Observed by LIGO and Virgo during the First and Second Observing Runs

We present the results from three gravitational-wave searches for coalescing compact binaries with component masses above 1  M⊙ during the first and second observing runs of the advanced gravitational-wave detector network. During the first observing run (O1), from September 12, 2015 to January 19, 2016, gravitational waves from three binary black hole mergers were detected. The second observing run (O2), which ran from November 30, 2016 to August 25, 2017, saw the first detection of gravitational waves from a binary neutron star inspiral, in addition to the observation of gravitational waves from a total of seven binary black hole mergers, four of which we report here for the first time: GW170729, GW170809, GW170818, and GW170823. For all significant gravitational-wave events, we provide estimates of the source properties. The detected binary black holes have total masses between 18.6−0.7+3.2  M⊙ and 84.4−11.1+15.8  M⊙ and range in distance between 320−110+120 and 2840−1360+1400  Mpc. No neutron star-black hole mergers were detected. In addition to highly significant gravitational-wave events, we also provide a list of marginal event candidates with an estimated false-alarm rate less than 1 per 30 days. From these results over the first two observing runs, which include approximately one gravitational-wave detection per 15 days of data searched, we infer merger rates at the 90% confidence intervals of 110−3840  Gpc−3 y−1 for binary neutron stars and 9.7−101  Gpc−3 y−1 for binary black holes assuming fixed population distributions and determine a neutron star-black hole merger rate 90% upper limit of 610  Gpc−3 y−1

Properties of the Binary Neutron Star Merger GW170817

On August 17, 2017, the Advanced LIGO and Advanced Virgo gravitational-wave detectors observed a low-mass compact binary inspiral. The initial sky localization of the source of the gravitational-wave signal, GW170817, allowed electromagnetic observatories to identify NGC 4993 as the host galaxy. In this work, we improve initial estimates of the binary's properties, including component masses, spins, and tidal parameters, using the known source location, improved modeling, and recalibrated Virgo data. We extend the range of gravitational-wave frequencies considered down to 23 Hz, compared to 30 Hz in the initial analysis. We also compare results inferred using several signal models, which are more accurate and incorporate additional physical effects as compared to the initial analysis. We improve the localization of the gravitational-wave source to a 90% credible region of 16  deg2. We find tighter constraints on the masses, spins, and tidal parameters, and continue to find no evidence for nonzero component spins. The component masses are inferred to lie between 1.00 and 1.89  M⊙ when allowing for large component spins, and to lie between 1.16 and 1.60  M⊙ (with a total mass 2.73−0.01+0.04  M⊙) when the spins are restricted to be within the range observed in Galactic binary neutron stars. Using a precessing model and allowing for large component spins, we constrain the dimensionless spins of the components to be less than 0.50 for the primary and 0.61 for the secondary. Under minimal assumptions about the nature of the compact objects, our constraints for the tidal deformability parameter Λ are (0,630) when we allow for large component spins, and 300−230+420 (using a 90% highest posterior density interval) when restricting the magnitude of the component spins, ruling out several equation-of-state models at the 90% credible level. Finally, with LIGO and GEO600 data, we use a Bayesian analysis to place upper limits on the amplitude and spectral energy density of a possible postmerger signal

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

Search for eccentric binary black hole mergers with Advanced LIGO and Advanced Virgo during their first and second observing runs

When formed through dynamical interactions, stellar-mass binary black holes (BBHs) may retain eccentric orbits (e > 0.1 at 10 Hz) detectable by ground-based gravitational-wave detectors. Eccentricity can therefore be used to differentiate dynamically formed binaries from isolated BBH mergers. Current template-based gravitational-wave searches do not use waveform models associated with eccentric orbits, rendering the search less efficient for eccentric binary systems. Here we present the results of a search for BBH mergers that inspiral in eccentric orbits using data from the first and second observing runs (O1 and O2) of Advanced LIGO and Advanced Virgo. We carried out the search with the coherent WaveBurst algorithm, which uses minimal assumptions on the signal morphology and does not rely on binary waveform templates. We show that it is sensitive to binary mergers with a detection range that is weakly dependent on eccentricity for all bound systems. Our search did not identify any new binary merger candidates. We interpret these results in light of eccentric binary formation models. We rule out formation channels with rates greater than about 100 Gpc−3 yr−1 for e > 0.1, assuming a black hole mass spectrum with a power-law index less than about 2