Summary
Background
Real‐world biologic drug survival is an important proxy measure for effectiveness. Predictors of drug survival may help patients with psoriasis choose between biologic therapies.
...Objectives
(i) To assess the relative drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis. (ii) To investigate predictors of biologic drug survival.
Methods
A prospective cohort study was performed in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2019. We performed survival analysis and fitted a flexible parametric survival model for biologic discontinuation due to ineffectiveness.
Results
In total 9652 patients were included: 5543 starting on adalimumab (57·4%), 991 on secukinumab (10·3%) and 3118 on ustekinumab (32·3%). The overall drug survivals of adalimumab, secukinumab and ustekinumab in year 1 were 0·78 95% confidence interval (CI) 0·77–0·79, 0·88 (95% CI 0·86–0·91) and 0·88 (95% CI 0·87–0·89), respectively. The adjusted hazard ratios (adjHRs) for discontinuation of adalimumab and secukinumab compared with ustekinumab were 2·11 (95% CI 1·76–2·54) and 0·67 (95% CI 0·40–1·11), respectively. The presence of psoriatic arthritis predicted for survival in the adalimumab and secukinumab cohorts (adjHR 0·67, 95% CI 0·51–0·88 and 0·70, 95% CI 0·40–1·24, respectively), but for discontinuation in the ustekinumab cohort (adjHR 1·42, 95% CI 1·12–1·81). Previous exposure to biologic therapies predicted for discontinuation in the ustekinumab and secukinumab cohorts (adjHR 1·54, 95% CI 1·26–1·89 and 1·49, 95% CI 0·91–2·45, respectively) and for survival in the adalimumab cohort (adjHR 0·71, 95% CI 0·55–0·92).
Conclusions
Secukinumab and ustekinumab have similar sustained drug survival, while adalimumab has a lower drug survival in patients with psoriasis. Psoriatic arthritis and previous biologic experience were predictors with differential effects between the biologic therapies.
What is already known about this topic?
There is conflicting evidence over the real‐world drug survival of secukinumab in patients with psoriasis.
Data from registries to date suggest that secukinumab has a lower drug survival than that reported from clinical trials.
What does this study add?
This study found that secukinumab and ustekinumab had similar sustained drug survival in the real world, while the drug survival of adalimumab was lower, suggesting that the real‐world drug survival of secukinumab is higher than previously reported.
We found that psoriatic arthritis and previous biologic experience had differential effects on drug discontinuation in the three biologic cohorts. These predictors may help patients and clinicians choose the most appropriate biologic therapy.
Linked Comment: Veysey. Br J Dermatol 2020; 183:204–205.
We present an analysis of the luminosity distances of Type Ia Supernovae (SNe) from the Sloan Digital Sky Survey-II (SDSS-II) SN Survey in conjunction with other intermediate-redshift (z < 0.4) ...cosmological measurements including redshift-space distortions from the Two-Degree Field Galaxy Redshift Survey (2dFGRS), the integrated Sachs–Wolfe (ISW) effect seen by the SDSS and the latest baryon acoustic oscillation (BAO) distance scale from both the SDSS and 2dFGRS. We have analysed the SDSS-II SN data alone using a variety of ‘model-independent’ methods and find evidence for an accelerating Universe at a >97 per cent level from this single data set. We find good agreement between the SN and BAO distance measurements, both consistent with a Λ-dominated cold dark matter cosmology, as demonstrated through an analysis of the distance duality relationship between the luminosity (dL) and angular diameter (dA) distance measures. We then use these data to estimate w within this restricted redshift range (z < 0.4). Our most stringent result comes from the combination of all our intermediate-redshift data (SDSS-II SNe, BAO, ISW and redshift-space distortions), giving w=−0.81+0.16−0.18 (stat) ± 0.15 (sys) and ΩM= 0.22+0.09−0.08 assuming a flat universe. This value of w and associated errors only change slightly if curvature is allowed to vary, consistent with constraints from the cosmic microwave background. We also consider more limited combinations of the geometrical (SN, BAO) and dynamical (ISW, redshift-space distortions) probes.
We present a study of the low-frequency radio properties of broad absorption line quasars (BALQSOs) from the LOFAR Two-metre Sky-Survey Data Release 1 (LDR1). The value-added LDR1 catalogue contains ...Pan-STARRS counterparts, which we match with the Sloan Digital Sky Survey (SDSS) DR7 and DR12 quasar catalogues. We find that BALQSOs are twice as likely to be detected at 144 MHz than their non-BAL counterparts, and BALQSOs with low-ionisation species present in their spectra are three times more likely to be detected than those with only high-ionisation species. The BALQSO fraction at 144 MHz is constant with increasing radio luminosity, which is inconsistent with previous results at 1.4 GHz, indicating that observations at the different frequencies may be tracing different sources of radio emission. We cross-match radio sources between the Faint Images of the Radio Sky at Twenty Centimeters (FIRST) survey and LDR1, which provides a bridge via the LDR1 Pan-STARRS counterparts to identify BALQSOs in SDSS. Consequently we expand the sample of BALQSOs detected in FIRST by a factor of three. The LDR1-detected BALQSOs in our sample are almost exclusively radio-quiet (log(R144 MHz) < 2), with radio sizes at 144 MHz typically less than 200 kpc; these radio sizes tend to be larger than those at 1.4 GHz, suggesting more extended radio emission at low frequencies. We find that although the radio detection fraction increases with increasing balnicity index (BI), there is no correlation between BI and either low-frequency radio power or radio-loudness. This suggests that both radio emission and BI may be linked to the same underlying process, but are spatially distinct phenomena.
The nature and role of the binary companion of carbon-oxygen white dwarf stars that explode as Type Ia supernovae (SNe Ia) are not yet fully understood. Past detections of circumstellar material ...(CSM) that contain hydrogen for a small number of SN Ia progenitor systems suggest that at least some have a nondegenerate companion. In order to constrain the prevalence, location, and quantity of CSM in SN Ia systems, we performed a near-ultraviolet (NUV) survey with the Hubble Space Telescope (HST) to look for the high-energy signature of SN Ia ejecta interacting with the CSM. Our survey revealed that SN 2015cp, an SN 1991T-like overluminous SN Ia, was experiencing late-onset interaction between its ejecta and the surrounding CSM 664 days after its light-curve peak. We present ground- and space-based follow-up observations of SN 2015cp that reveal optical emission lines of H and Ca, typical signatures of ejecta-CSM interaction. We show how SN 2015cp was likely similar to the well-studied SN Ia-CSM event PTF11kx, making it the second case in which an unambiguously classified SN Ia was observed to interact with a distant shell of CSM that contains hydrogen (RCSM 1016 cm). The remainder of our HST NUV images of SNe Ia were nondetections that we use to constrain the occurrence rate of observable late-onset CSM interaction. We apply theoretical models for the emission from ejecta-CSM interaction to our NUV nondetections and place upper limits on the mass and radial extent of CSM in SN Ia progenitor systems.
Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems ...arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles
. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states
. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.
Indistinguishability of particles is a fundamental principle of quantum mechanics
. For all elementary and quasiparticles observed to date-including fermions, bosons and Abelian anyons-this principle ...guarantees that the braiding of identical particles leaves the system unchanged
. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions
. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well-developed mathematical description of non-Abelian anyons and numerous theoretical proposals
, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. Whereas efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasiparticles, superconducting quantum processors allow for directly manipulating the many-body wavefunction by means of unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons
, we implement a generalized stabilizer code and unitary protocol
to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of using the anyons for quantum computation and use braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and, through the future inclusion of error correction to achieve topological protection, could open a path towards fault-tolerant quantum computing.
Summary Sarcopenic obesity (SO) is assuming a prominent role as a risk factor because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). The ...increase in obesity prevalence rates in older subjects is of concern given the associated disease risks and more limited therapeutic options available in this age group. This review has two main objectives. The primary objective is to collate results from studies investigating the effects of SO on physical and cardio-metabolic functions. The secondary objective is to evaluate published studies for consistency in methodology, diagnostic criteria, exposure and outcome selection. Large between-study heterogeneity was observed in the application of diagnostic criteria and choice of body composition components for the assessment of SO, which contributes to the inconsistent associations of SO with cardio-metabolic outcomes. We propose a metabolic load:capacity model of SO given by the ratio between fat mass and fat free mass, and discuss how this could be operationalised. The concept of regional fat distribution could be incorporated into the model and tested in future studies to advance our understanding of SO as a predictor of risk for cardio-metabolic diseases and physical disability.
Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic ...pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments-such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons-suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 °C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.
Objective
Changes in the partitioning of dissolved inorganic (DIC) and glucose were elucidated by utilising
13
C labelled DIC or glucose, and quantifying the biochemical profile of mixotrophic, ...heterotrophic and photoautotrophic cultures of the microalga
Tetraselmis suecica
.
Results
Mixotrophic cultivation increases microalgal productivity and changes their biochemical profile, due to an alteration in the partitioning of carbon within the cell. When cultured mixotrophically and heterotrophically, there is enhanced incorporation of carbon into shorter chain saturated fatty acids and non-lipid biomass, compared to photoautotrophic cultivation. Autotrophic culture results in increased total fatty acid content of cultures (4.19% dry weight compared to 2.13%) and shifts the fatty acid profile in favour of long-chain unsaturated fatty acids, such as 18:2 n-(9,12), compared to mixotrophic culture. Quantifying the changes in partitioning between DIC and glucose facilitates tailoring of the biochemical profile to develop “designer” algae.
Conclusions
There is a condition specific shift in carbon partitioning into different fatty acid and biochemical fractions in
T. suecica
, with more inorganic carbon partitioned into 18:2 n-(9,12) in photoautotrophic rather than mixotrophic cultures.
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