Shared decision-making interventions in the choice of antipsychotic prescription in people living with psychosis (SHAPE):Protocol for a realist review

Background: Shared decision-making (SDM) has yet to be successfully adopted into routine use in psychiatric settings amongst people living with severe mental illnesses. Suboptimal rates of SDM are particularly prominent amongst patients with psychotic illnesses during antipsychotic treatment choices. Many interventions have been assessed for their efficacy in improving SDM within this context, although results have been variable and inconsistent. Aims: To generate an in-depth understanding of how, why, for whom, and to what extent interventions facilitating the application of SDM during antipsychotic treatment choices work and the impact of contextual factors on intervention effectiveness. Methods: This review will use realist review methodology to provide a causal understanding of how and why interventions work when implementing SDM during antipsychotic treatment choices. The cohort of interest will be those experiencing psychosis where ongoing treatment with an antipsychotic is clinically indicated. The review will take place over five stages; (1) Locating existing theories, (2) Searching for evidence, (3) Selecting articles, (4) Extracting and organising data and (5) Synthesizing evidence and drawing conclusions. An understanding of how and why interventions work will be achieved by developing realist programme theories on intervention effectiveness through iterative literature reviews and engaging with various stakeholder groups, including patient, clinician and carer representatives. Discussion: This is the first realist review aiming to identify generative mechanisms explaining how and why successful interventions aimed at improving SDM within the parameters outlined work and in which contexts desired outcomes are most likely to be achieved. Review findings will include suggestions for clinicians, policy and decision-makers about the most promising interventions to pursue and their ideal attributes

Safety culture in a major accredited Irish university teaching hospital: a mixed methods study using the safety attitudes questionnaire.

Background: The measurement of safety culture, the way in which members of an organisation think about and prioritise safety, in a hospital can provide valuable insight and inform quality improvement strategies. Aims: The aim of this study is to describe the safety culture of a university teaching hospital in the Republic of Ireland. Methods: This is a mixed methods survey study using the Safety Attitudes Questionnaire (SAQ). The SAQ was distributed to all staff in the study hospital. Staff attitudes towards six domains of patient safety culture were assessed over 32 Likert-scaled items. Thematic analysis was performed on qualitative data. Results: A total of 768 staff members completed and returned a copy of the SAQ. The hospital scored above the international benchmark in five out of six domains, indicating a positive safety culture, but scored below the international benchmark in the domain 'Working Conditions'. This positive safety culture was not mirrored in the qualitative data, from which five themes emerged; three major-Staffing Issues, Patient-Focused Care and Hospital Environment-and two minor-Safe Reporting Culture and Training and Education. Conclusions: In this study, a mixed methods approach was successfully used to investigate the safety culture in a large Irish hospital. Although the SAQ results indicated a positive safety culture, the qualitative data revealed a number of issues that the hospital staff felt impacted negatively on patient safety. The results of this study will inform future work on the design of an intervention to improve patient safety in the hospital

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

The Simons Observatory microwave SQUID multiplexing detector module design

Advances in cosmic microwave background (CMB) science depend on increasing the number of sensitive detectors observing the sky. New instruments deploy large arrays of superconducting transition-edge sensor (TES) bolometers tiled densely into ever larger focal planes. High multiplexing factors reduce the thermal loading on the cryogenic receivers and simplify their design. We present the design of focal-plane modules with an order of magnitude higher multiplexing factor than has previously been achieved with TES bolometers. We focus on the novel cold readout component, which employs microwave SQUID multiplexing ($\mu$mux). Simons Observatory will use 49 modules containing 60,000 bolometers to make exquisitely sensitive measurements of the CMB. We validate the focal-plane module design, presenting measurements of the readout component with and without a prototype detector array of 1728 polarization-sensitive bolometers coupled to feedhorns. The readout component achieves a $95\%$ yield and a 910 multiplexing factor. The median white noise of each readout channel is 65 $\mathrm{pA/\sqrt{Hz}}$. This impacts the projected SO mapping speed by $< 8\%$, which is less than is assumed in the sensitivity projections. The results validate the full functionality of the module. We discuss the measured performance in the context of SO science requirements, which are exceeded.Comment: Accepted to The Astrophysical Journa

The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

We present new measurements of cosmic microwave background (CMB) lensing over $9400$ sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at $2.3\%$ precision ($43\sigma$ significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of $A_{\mathrm{lens}}=1.013\pm0.023$ relative to the Planck 2018 CMB power spectra best-fit $\Lambda$CDM model and $A_{\mathrm{lens}}=1.005\pm0.023$ relative to the $\text{ACT DR4} + \text{WMAP}$ best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination $S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25}$ of $S^{\mathrm{CMBL}}_8= 0.818\pm0.022$ from ACT DR6 CMB lensing alone and $S^{\mathrm{CMBL}}_8= 0.813\pm0.018$ when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with $\Lambda$CDM model constraints from Planck or $\text{ACT DR4} + \text{WMAP}$ CMB power spectrum measurements. Our lensing measurements from redshifts $z\sim0.5$--$5$ are thus fully consistent with $\Lambda$CDM structure growth predictions based on CMB anisotropies probing primarily $z\sim1100$. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky

Observations of the millimeter sky contain valuable information on a number of signals, including the blackbody cosmic microwave background (CMB), Galactic emissions, and the Compton-$y$ distortion due to the thermal Sunyaev-Zel'dovich (tSZ) effect. Extracting new insight into cosmological and astrophysical questions often requires combining multi-wavelength observations to spectrally isolate one component. In this work, we present a new arcminute-resolution Compton-$y$ map, which traces out the line-of-sight-integrated electron pressure, as well as maps of the CMB in intensity and E-mode polarization, across a third of the sky (around 13,000 sq.~deg.). We produce these through a joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release 4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We present detailed verification of an internal linear combination pipeline implemented in a needlet frame that allows us to efficiently suppress Galactic contamination and account for spatial variations in the ACT instrument noise. These maps provide a significant advance, in noise levels and resolution, over the existing \textit{Planck} component-separated maps and will enable a host of science goals including studies of cluster and galaxy astrophysics, inferences of the cosmic velocity field, primordial non-Gaussianity searches, and gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly available upon publication of the paper. The CMB T and E mode maps will be made available when the DR6 maps are made publi

The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters

We present cosmological constraints from a gravitational lensing mass map covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO measurements (from SDSS and 6dF), we obtain the amplitude of matter fluctuations $\sigma_8 = 0.819 \pm 0.015$ at 1.8% precision, $S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.840\pm0.028$ and the Hubble constant $H_0= (68.3 \pm 1.1)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}$ at 1.6% precision. A joint constraint with CMB lensing measured by the Planck satellite yields even more precise values: $\sigma_8 = 0.812 \pm 0.013$, $S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.831\pm0.023$ and $H_0= (68.1 \pm 1.0)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}$. These measurements agree well with $\Lambda$CDM-model extrapolations from the CMB anisotropies measured by Planck. To compare these constraints to those from the KiDS, DES, and HSC galaxy surveys, we revisit those data sets with a uniform set of assumptions, and find $S_8$ from all three surveys are lower than that from ACT+Planck lensing by varying levels ranging from 1.7-2.1$\sigma$. These results motivate further measurements and comparison, not just between the CMB anisotropies and galaxy lensing, but also between CMB lensing probing $z\sim 0.5-5$ on mostly-linear scales and galaxy lensing at $z\sim 0.5$ on smaller scales. We combine our CMB lensing measurements with CMB anisotropies to constrain extensions of $\Lambda$CDM, limiting the sum of the neutrino masses to $\sum m_{\nu} < 0.12$ eV (95% c.l.), for example. Our results provide independent confirmation that the universe is spatially flat, conforms with general relativity, and is described remarkably well by the $\Lambda$CDM model, while paving a promising path for neutrino physics with gravitational lensing from upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological likelihood data is here: https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also see companion papers Qu et al and MacCrann et al. Mass maps will be released when papers are publishe

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders