Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding ...obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years.
Maternal/infant dyads (n=62) born ⩽30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment.
Maternal obesity was associated with positive screen for autism (odds ratio=9.88, P=0.002) and lower composite language scores (β=-9.36, (confidence interval=-15.11, -3.61), P=0.002).
Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity.
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.
Summary
Background
Biologic therapies have revolutionized the treatment of moderate‐to‐severe psoriasis. However, for reasons largely unknown, many patients do not respond or lose response to these ...drugs.
Objectives
To evaluate demographic, social and clinical factors that could be used to predict effectiveness and stratify response to biologic therapies in psoriasis.
Methods
Using a multicentre, observational, prospective pharmacovigilance study (BADBIR), we identified biologic‐naive patients starting biologics with outcome data at 6 (n = 3079) and 12 (n = 3110) months. Associations between 31 putative predictors and outcomes were investigated in univariate and multivariable regression analyses. Potential stratifiers of treatment response were investigated with statistical interactions.
Results
Eight factors associated with reduced odds of achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) at 6 months were identified (described as odds ratio and 95% confidence interval): demographic (female sex, 0·78, 0·66–0·93); social (unemployment, 0·67, 0·45–0·99); unemployment due to ill health (0·62, 0·48–0·82); ex‐ and current smoking (0·81, 0·66–0·99 and 0·79, 0·63–0·99, respectively); clinical factors (high weight, 0·99, 0·99–0·99); psoriasis of the palms and/or soles (0·75, 0·61–0·91); and presence of small plaques only compared with small and large plaques (0·78, 0·62–0·96). White ethnicity (1·48, 1·12–1·97) and higher baseline PASI (1·04, 1·03–1·04) were associated with increased odds of achieving PASI 90. The findings were largely consistent at 12 months. There was little evidence for predictors of differential treatment response.
Conclusions
Psoriasis phenotype and potentially modifiable factors are associated with poor outcomes with biologics, underscoring the need for lifestyle management. Effect sizes suggest that these factors alone cannot inform treatment selection.
What's already known about this topic?
Biologic therapy used in the treatment of moderate‐to‐severe psoriasis differs in its effectiveness across patients.
Previous research has indicated that patients with a higher body mass index, who smoke or who have smoked, and with a lower baseline Psoriasis Area and Severity Index (PASI) are less likely to have a good outcome with biologic therapy for the treatment of moderate‐to‐severe psoriasis.
What does this study add?
This large‐scale study in a real‐world setting confirms that weight, smoking status and baseline PASI are associated with effectiveness of biologic therapy.
There is evidence that non‐white ethnicity, female sex, unemployment, psoriasis of the palms and soles and the presence of small chronic plaques are associated with poor outcomes with biologics.
There is some evidence that men have a comparatively worse response to etanercept, relative to adalimumab, than women. Otherwise, most factors do not appear to be predictors of differential treatment response.
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Porphyromonas, Tannerella, and Prevotella species found in severe periodontitis use the Type IX Secretion System (T9SS) to load their outer membrane surface with an array of virulence factors. These ...virulence factors are then released on outer membrane vesicles (OMVs), which penetrate the host to dysregulate the immune response to establish a positive feedback loop of chronic, inflammatory destruction of the tooth’s supporting tissues. In this review, we present the latest information on the molecular architecture of the T9SS and provide mechanistic insight into its role in secretion and attachment of cargo proteins to produce a virulence coat on cells and OMVs. The recent molecular structures of the T9SS motor comprising PorL and PorM as well as the secretion pore Sov, together with advances in the overall interactome, have provided insight into the possible mechanisms of secretion. We propose the presence of PorL/M motors arranged in a circle at the inner membrane with bent periplasmic rotors interacting with the PorN protein. At the outer membrane, we envisage a slide carousel model where the PorN protein is driven around a circular track composed of PorK. Cargo proteins are transported by PorN to PorW and the Sov translocon just as slides are rotated to the projection window. Secreted proteins are proposed to then be shuttled along highways consisting of the PorV shuttle protein to an array of attachment complexes distributed around the cell. The cell surface attachment of cargo is a hallmark of the T9SS, and in Porphyromonas gingivalis and Tannerella forsythia, this attachment is achieved via covalent bonding to a linking sugar synthesized by the Wbp/Vim pathway. The cell-surface attached cargo are enriched on OMVs, which are then released from the cell.
ABSTRACT
We present the discovery with Keck of the extremely infrared (IR) luminous transient AT 2017gbl, coincident with the Northern nucleus of the luminous infrared galaxy (LIRG) IRAS 23436+5257. ...Our extensive multiwavelength follow-up spans ∼900 d, including photometry and spectroscopy in the optical and IR, and (very long baseline interferometry) radio and X-ray observations. Radiative transfer modelling of the host galaxy spectral energy distribution and long-term pre-outburst variability in the mid-IR indicate the presence of a hitherto undetected dust obscured active galactic nucleus (AGN). The optical and near-IR spectra show broad ∼2000 km s−1 hydrogen, He i, and O i emission features that decrease in flux over time. Radio imaging shows a fast evolving compact source of synchrotron emission spatially coincident with AT 2017gbl. We infer a lower limit for the radiated energy of 7.3 × 1050 erg from the IR photometry. An extremely energetic supernova would satisfy this budget, but is ruled out by the radio counterpart evolution. Instead, we propose AT 2017gbl is related to an accretion event by the central supermassive black hole, where the spectral signatures originate in the AGN broad line region and the IR photometry is consistent with re-radiation by polar dust. Given the fast evolution of AT 2017gbl, we deem a tidal disruption event (TDE) of a star a more plausible scenario than a dramatic change in the AGN accretion rate. This makes AT 2017gbl the third TDE candidate to be hosted by a LIRG, in contrast to the so far considered TDE population discovered at optical wavelengths and hosted preferably by post-starburst galaxies.
Summary
Background Multiple questionnaires to screen for psoriatic arthritis (PsA) have been developed but the optimal screening questionnaire is unknown.
Objectives To compare three PsA screening ...questionnaires in a head‐to‐head study using CASPAR (the Classification Criteria for Psoriatic Arthritis) as the gold standard.
Methods This study recruited from 10 U.K. secondary care dermatology clinics. Patients with a diagnosis of psoriasis, not previously diagnosed with PsA, were given all three questionnaires. All patients who were positive on any questionnaire were invited for a rheumatological assessment. Receiver operating characteristic (ROC) curves were used to compare the sensitivity, specificity and area under the curve of the three questionnaires according to CASPAR criteria.
Results In total, 938 patients with psoriasis were invited to participate and 657 (70%) patients returned the questionnaires. One or more questionnaires were positive in 314 patients (48%) and 195 (62%) of these patients attended for assessment. Of these, 47 patients (24%) were diagnosed with PsA according to the CASPAR criteria. The proportion of patients with PsA increased with the number of positive questionnaires (one questionnaire, 19·1%; two, 34·0%; three, 46·8%). Sensitivities and specificities for the three questionnaires, and areas under the ROC curve were, respectively: Psoriatic Arthritis Screening Evaluation (PASE), 74·5%, 38·5%, 0·594; Psoriasis Epidemiology Screening Tool (PEST), 76·6%, 37·2%, 0·610; Toronto Psoriatic Arthritis Screen (ToPAS), 76·6%, 29·7%, 0·554. The majority of patients with a false positive response had degenerative or osteoarthritis.
Conclusion Although the PEST and ToPAS questionnaires performed slightly better than the PASE questionnaire at identifying PsA, there is little difference between these instruments. These screening tools identify many cases of musculoskeletal disease other than PsA.
What’s already known about this topic?
•
A number of screening questionnaires have been developed to detect psoriatic arthritis in people with psoriasis.
•
Each questionnaire has shown good and largely equivalent performance, in terms of specificity and sensitivity, in the development cohorts.
•
What is needed is a head‐to‐head study in a new cohort of patients with psoriasis.
What does this study add?
•
Each of the questionnaires performed worse in this new cohort of patients in secondary care, with no significant differences between them.
•
Both sensitivity and specificity were worse, although the study design was likely to underestimate the specificity and overestimate the sensitivity.
•
Screening questionnaires such as these will detect other musculoskeletal diseases in addition to psoriatic arthritis and additional information may be needed to enhance their specificity.
Magnetospheric accretion models predict that matter from protoplanetary disks accretes onto stars via funnel flows, which follow stellar magnetic field lines and shock on the stellar surfaces
, ...leaving hot spots with density gradients
. Previous work has provided observational evidence of varying density in hot spots
, but these observations were not sensitive to the radial density distribution. Attempts have been made to measure this distribution using X-ray observations
; however, X-ray emission traces only a fraction of the hot spot
and also coronal emission
. Here we report periodic ultraviolet and optical light curves of the accreting star GM Aurigae, which have a time lag of about one day between their peaks. The periodicity arises because the source of the ultraviolet and optical emission moves into and out of view as it rotates along with the star. The time lag indicates a difference in the spatial distribution of ultraviolet and optical brightness over the stellar surface. Within the framework of a magnetospheric accretion model, this finding indicates the presence of a radial density gradient in a hot spot on the stellar surface, because regions of the hot spot with different densities have different temperatures and therefore emit radiation at different wavelengths.
It is currently not well known how coherent carbon and oxygen isotope chronologies from different species and sites are under temperate climate conditions. Here we investigated nine chronologies from ...Switzerland covering the last two centuries, including three deciduous species (Fagus sylvatica, Fraxinus excelsior, and Quercus petraea) and three conifer species (Abies alba, Picea abies, and Pinus sylvestris) from sites neither strongly limited by temperature nor precipitation. All of the chronologies except Fraxinus were significantly correlated to at least one other chronology. Correlations between different species of the same site were of similar strength to correlations between the sites. We observed a strong common high‐frequency (interannual) signal for the δ13C chronologies, whereas the low‐frequency (decadal‐scale) signal was more similar among the δ18O chronologies. For both carbon and oxygen isotopes, we found significant positive relationships with annual and growing season temperatures and negative relationships with precipitation, again of similar magnitude for all species except for Fraxinus, which contained only minor climatic information. Averaging of all chronologies resulted in an increase in the climatic signal of the mean chronology. The combined δ18O record reflected decadal‐scale temperature variations remarkably well (r = 0.72). However, the relationship between climate and carbon isotopes declined over the last 3 decades of the 20th century, probably related to the steep increase in atmospheric CO2 concentrations, resulting in strongly diverging δ13C trends of the different chronologies. Our study indicates that combining chronologies from different species enhances the potential of isotope studies for extending climate reconstructions into areas of temperate climate.
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