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

Woman-Centered Design through Humanity, Activism, and Inclusion

Women account for over half of the global population, however, continue to be subject to systematic and systemic disadvantage, particularly in terms of access to health and education. At every intersection, where systemic inequality accounts for greater loss of life or limitations on full and healthy living, women are more greatly impacted by those inequalities. The design of technologies is no different, the very definition of technology is historically cast in terms of male activities, and advancements in the field are critical to improve women's quality of life. This article views HCI, a relatively new field, as well positioned to act critically in the ways that technology serve, refigure, and redefine women's bodies. Indeed, the female body remains a contested topic, a restriction to the development of women's health. On one hand, the field of women's health has attended to the medicalization of the body and therefore is to be understood through medical language and knowledge. On the other hand, the framing of issues associated with women's health and people's experiences of and within such system(s) remain problematic for many. This is visible today in, e.g., socio-cultural practices in disparate geographies or medical devices within a clinic or the home. Moreover, the biological body is part of a great unmentionable, i.e., the perils of essentialism. We contend that it is necessary, pragmatically and ethically, for HCI to turn its attention toward a woman-centered design approach. While previous research has argued for the dangers of gender-demarcated design work, we advance that designing for and with women should not be regarded as ghettoizing, but instead as critical to improving women's experiences in bodily transactions, choices, rights, and access to and in health and care. In this article, we consider how and why designing with and for woman matters. We use our design-led research as a way to speak to and illustrate alternatives to designing for and with women within HCI.QC 20200930</p

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

The atacama cosmology telescope: lensing of CMB temperature and polarization derived from cosmic infrared background cross-correlation

We present a measurement of the gravitational lensing of the Cosmic Microwave Background (CMB) temperature and polarization fields obtained by cross-correlating the reconstructed convergence signal from the first season of Atacama Cosmology Telescope Polarimeter data at 146 GHz with Cosmic Infrared Background (CIB) fluctuations measured using the Planck satellite. Using an effective overlap area of 92.7 square degrees, we detect gravitational lensing of the CMB polarization by large-scale structure at a statistical significance of $4.5\sigma$. Combining both CMB temperature and polarization data gives a lensing detection at $9.1\sigma$ significance. A B-mode polarization lensing signal is present with a significance of $3.2\sigma$. We also present the first measurement of CMB lensing–CIB correlation at small scales corresponding to $l\gt 2000$. Null tests and systematic checks show that our results are not significantly biased by astrophysical or instrumental systematic effects, including Galactic dust. Fitting our measurements to the best-fit lensing-CIB cross-power spectrum measured in Planck data, scaled by an amplitude A, gives $A={1.02}_{-0.08}^{+0.12}$(stat.) ± 0.06(syst.), consistent with the Planck results

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there is significantly enriched connectivity among the proteins encoded by genes harboring de novo missense or nonsense mutations, and excess connectivity to prior ASD genes of major effect, suggesting a subset of observed events are relevant to ASD risk. The small increase in rate of de novo events, when taken together with the connections among the proteins themselves and to ASD, are consistent with an important but limited role for de novo point mutations, similar to that documented for de novo copy number variants. Genetic models incorporating these data suggest that the majority of observed de novo events are unconnected to ASD, those that do confer risk are distributed across many genes and are incompletely penetrant (i.e., not necessarily causal). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors

The Atacama Cosmology Telescope: Modeling the Gas Thermodynamics in BOSS CMASS galaxies from Kinematic and Thermal Sunyaev-Zel'dovich Measurements

The thermal and kinematic Sunyaev-Zel'dovich effects (tSZ, kSZ) probe the thermodynamic properties of the circumgalactic and intracluster medium (CGM and ICM) of galaxies, groups, and clusters, since they are proportional, respectively, to the integrated electron pressure and momentum along the line-of-sight. We present constraints on the gas thermodynamics of CMASS galaxies in the Baryon Oscillation Spectroscopic Survey (BOSS) using new measurements of the kSZ and tSZ signals obtained in a companion paper. Combining kSZ and tSZ measurements, we measure within our model the amplitude of energy injection $\epsilon M_\star c^2$, where $M_\star$ is the stellar mass, to be $\epsilon=(40\pm9)\times10^{-6}$, and the amplitude of the non-thermal pressure profile to be $\alpha_{\rm Nth}<0.2$ (2$\sigma$), indicating that less than 20% of the total pressure within the virial radius is due to a non-thermal component. We estimate the effects of including baryons in the modeling of weak-lensing galaxy cross-correlation measurements using the best fit density profile from the kSZ measurement. Our estimate reduces the difference between the original theoretical model and the weak-lensing galaxy cross-correlation measurements in arXiv:1611.08606 by half, but does not fully reconcile it. Comparing the kSZ and tSZ measurements to cosmological simulations, we find that they under predict the CGM pressure and to a lesser extent the CGM density at larger radii. This suggests that the energy injected via feedback models in the simulations that we compared against does not sufficiently heat the gas at these radii. We do not find significant disagreement at smaller radii. These measurements provide novel tests of current and future simulations. This work demonstrates the power of joint, high signal-to-noise kSZ and tSZ observations, upon which future cross-correlation studies will improve.Comment: Accepted for publication in Physical Review D. Editors' Suggestion. New Fig. 1-2, Tab.

The Atacama Cosmology Telescope: CMB Polarization at 200<ℓ<9000200<\ell<9000

We report on measurements of the cosmic microwave background (CMB) and celestial polarization at 146 GHz made with the Atacama Cosmology Telescope Polarimeter (ACTPol) in its first three months of observing. Four regions of sky covering a total of 270 square degrees were mapped with an angular resolution of $1.3'$. The map noise levels in the four regions are between 11 and 17 $\mu$K-arcmin. We present TT, TE, EE, TB, EB, and BB power spectra from three of these regions. The observed E-mode polarization power spectrum, displaying six acoustic peaks in the range $200<\ell<3000$, is an excellent fit to the prediction of the best-fit cosmological models from WMAP9+ACT and Planck data. The polarization power spectrum, which mainly reflects primordial plasma velocity perturbations, provides an independent determination of cosmological parameters consistent with those based on the temperature power spectrum, which results mostly from primordial density perturbations. We find that without masking any point sources in the EE data at $\ell<9000$, the Poisson tail of the EE power spectrum due to polarized point sources has an amplitude less than $2.4$ $\mu$K$^2$ at $\ell = 3000$ at 95\% confidence. Finally, we report that the Crab Nebula, an important polarization calibration source at microwave frequencies, has 8.7\% polarization with an angle of $150.7^\circ \pm 0.6^\circ$ when smoothed with a $5'$ Gaussian beam.Comment: 16 pages, 15 figures, 5 table