Absolute Area Research Articles

Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5Years: Pooled Analyses from the reSURFACE Pivotal Studies.

IntroductionTildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials.MethodsA 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population.ResultsThe proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg).ConclusionIn patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group.Trial registrationClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

33025 Stability of PASI

Background: Tildrakizumab, a high-affinity anti–interleukin 23p19 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis, has demonstrated efficacy and safety for up to 5 years. Absolute Psoriasis Area and Severity Index (PASI) <3 is considered a clinically relevant treatment target for moderate to severe plaque psoriasis. We determined the percentages of patients in the Phase 3 reSURFACE 1/2 (NCT01722331/NCT01729754) trials with PASI <3 at ≥80% and all follow-up visits up to week (W) 244. Methods: Methodology of these randomized controlled trials was previously published. At W64/W52, patients with at least a PASI 50 response entered an optional 4-year extension up to W256 (reSURFACE 1)/W244 (reSURFACE 2). Tildrakizumab 100 and 200 mg were administered at W0, W4, and every 12W thereafter. Study population included patients with PASI <3 at W28 (PASI <3 responders) who were randomized to continue treatment. Missing data were handled using multiple imputation. Results: At W28, 263 and 180 PASI <3 responders receiving tildrakizumab 100 and 200 mg, respectively, continued treatment. The mean (SD) numbers of visits with an absolute PASI <3 were 16.0 (3.5) and 16.6 (3.3) for tildrakizumab 100 and 200 mg, respectively; the median for both was 18.0. Among responders receiving tildrakizumab 100 and 200 mg, 80.2% and 87.2%, respectively, maintained PASI <3 response at ≥80% of follow-up visits and 58.9% and 70.0%, respectively, at all scheduled follow-up visits through W244. Conclusions: Tildrakizumab provided steady disease control over 5 years in most patients who were PASI <3 responders at W28.

Implications of climate change for environmental niche overlap between fiveCuscutapest species and their two main Leguminosae host crop species

AbstractSome parasitic plants are major pests in agriculture, but how this might be affected by climate change remains largely unknown. In this study, we assessed this question for five generalist holoparasiticCuscutaspecies (smoothseed alfalfa dodder [Cuscuta approximataBab.], alfalfa dodder [Cuscuta europaeaL.], soybean dodder [Cuscuta chinensisC. Wright], Peruvian dodder [Cuscuta australisR. Br.], and Japanese dodder [Cuscuta japonicaChoisy]) and two of their main Leguminosae host crop species (soybean [Glycine max(L.) Merr.] and alfalfa [Medicago sativaL.]. For each of the fiveCuscutaspecies and the two crop species, we ran MaxEnt models, using climatic and soil variables to predict their potential current distributions and potential future distributions for 2070. We ran species distribution models for all seven species for multiple climate change scenarios, and tested for changes in the overlap of suitable ranges of each crop with the five parasites. We found that annual mean temperature and isothermality are the main bioclimatic factors determining the suitable habitats of theCuscutaspecies and their hosts. For both host species, the marginally to optimally suitable area will increase by 2070 for all four representative concentration pathway scenarios. For most of theCuscutaspecies, the marginally to optimally suitable area will also increase. While the suitable areas for both the hosts and the parasites will increase overall, Schoener’sD, indicating the relative overlap in suitable area, will change only marginally. However, the absolute area of potential niche overlap may increase up to 6-fold by 2070. Overall, our results indicate that larger parts of the globe will become suitable for both host species, but that they could also suffer fromCuscutaparasitism in larger parts of their suitable ranges.

Isotope Ratio Outlier Analysis (IROA) for HPLC-TOFMS-Based Metabolomics of Human Urine.

Metabolic fingerprinting by mass spectrometry aims at the comprehensive, semiquantitative analysis of metabolites. Isotope dilution, if successfully implemented, may provide a more reliable, relative quantification. Therefore, the 13C labeled yeast extract of the IROA TruQuant kit was added as an internal standard (IS) to human urine samples measured in full-scan mode on a high-performance liquid chromatography-time-of-flight mass spectrometer (HPLC–TOFMS) system. The isotope ratio approach enabled the analysis of 112 metabolites. The correlation with reference data did not improve significantly using 12C/13C ratios compared to absolute 12C peak areas. Moreover, using an intricate 13C-labeled standard increased the complexity of the mass spectra, which made correct signal annotation more challenging. On the positive side, the ratio approach helps to reduce batch effects, but it does not perform better than computational methods such as the “removebatcheffect” function in the R package Limma.

Quantitative Indicators of Retraction Phenomenon on an Automated Breast Volume Scanner: Initial Study in the Diagnosis and Prognostic Prediction of Breast Tumors

Retraction phenomenon is a unique sign on an automated breast volume scanner coronal plane image and has high specificity in differentiating benign lesions from malignant breast cancer. The purpose of this study was to quantify the retraction phenomenon by setting different rules to describe connected regions from different dimensions. In total, six quantitative indicators (FΩ1,FΓ,FS,FΩ2,FΩ3and FL) were obtained. FΩ1, FΩ2 and FΩ3 represent the relative areas of the connected region under different rules. FΓandFS represent the number ratio and absolute area of the connected region, respectively. FL represents the ratio of edge numbers. Two hundred fourteen patients with 214 lesions (90 benign and 124 malignant) were enrolled in this study. All quantitative indicators in the malignant group were significantly higher than those in the benign group (all p values <0.001). The indicator FΓ achieved the highest area under the receiver operating characteristic curve (AUC) (0.701, 95% confidence interval: 0.631-0.771). Both FΓ and FS had significant associations with axillary lymph node metastasis (p=0.023 and 0.049). Compared with the classic texture feature gray-level co-occurrence matrix, retraction phenomenon quantization improved the AUC by 8.3%. The results indicate that retraction phenomenon quantitative indicators have certain value in distinguishing benign and malignant breast lesions and seem to be associated with axillary lymph node metastasis.

Functional traits influence patterns in vegetative and reproductive plant phenology - a multi-botanical garden study.

Phenology has emerged as key indicator of the biological impacts of climate change, yet the role of functional traits constraining variation in herbaceous species' phenology has received little attention. Botanical gardens are ideal places in which to investigate large numbers of species growing under common climate conditions. We ask whether interspecific variation in plant phenology is influenced by differences in functional traits. We recorded onset, end, duration and intensity of initial growth, leafing out, leaf senescence, flowering and fruiting for 212 species across five botanical gardens in Germany. We measured functional traits, including plant height, absolute and specific leaf area, leaf dry matter content, leaf carbon and nitrogen content and seed mass and accounted for species' relatedness. Closely related species showed greater similarities in timing of phenological events than expected by chance, but species' traits had a high degree of explanatory power, pointing to paramount importance of species' life-history strategies. Taller plants showed later timing of initial growth, and flowered, fruited and underwent leaf senescence later. Large-leaved species had shorter flowering and fruiting durations. Taller, large-leaved species differ in their phenology and are more competitive than smaller, small-leaved species. We assume climate warming will change plant communities' competitive hierarchies with consequences for biodiversity.

The effects of glucagon-like peptide-1 receptor agonists on adipose tissues in patients with type 2 diabetes: A meta-analysis of randomised controlled trials.

AimsGlucagon‑like peptide 1 receptor agonist (GLP-1RA) treatment can improve adipose distribution. We performed this meta-analysis to investigate whether GLP-1RAs preferentially reduce visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT) in patients with type 2 diabetes.Materials and methodsWe searched MEDLINE and the Cochrane Library for randomised controlled trials explicitly reporting changes in VAT and SAT. A random-effects model was performed to estimate the weighted mean difference (MD) for VAT and SAT. Heterogeneity among the studies was assessed using I2 statistics, and publication bias was assessed using Egger’s tests. Meta-regression was performed to identify the correlation between changes in adipose tissues and changes in body weight and glycated haemoglobin level.ResultsTen trials with 924 patients were enrolled in the meta-analysis. GLP-1RA treatment led to similar absolute area (cm2) reductions in VAT (MD -21.13 cm2, 95% CI [-29.82, -12.44]) and SAT (MD -22.89 cm2, 95% CI [-29.83, -15.95]). No significant publication bias was detected, and this result was stable in the sensitivity and subgroup analyses. Moreover, GLP-1RA treatment resulted in a greater reduction in VAT and SAT in the subgroup with a greater reduction in body weight. The absolute area reduction in VAT was significantly correlated with the reduction in body weight (r = 6.324, p = 0.035).ConclusionsGLP-1RA treatment leads to significant and similar absolute reductions in VAT and SAT, and the reduction in adipose tissues may be correlated with the reduction in body weight.

High-resolution label-free mapping of murine kidney vasculature by raster-scanning optoacoustic mesoscopy: an ex vivo study

BackgroundChronic kidney disease (CKD) is a global burden affecting both children and adults. Novel imaging modalities hold great promise to visualize and quantify structural, functional, and molecular organ damage. The aim of the study was to visualize and quantify murine renal vasculature using label-free raster scanning optoacoustic mesoscopy (RSOM) in explanted organs from mice with renal injury.Material and methodsFor the experiments, freshly bisected kidneys of alpha 8 integrin knock-out (KO) and wildtype mice (WT) were used. A total of n=7 female (n=4 KO, n=3 WT) and n=6 male animals (n=2 KO, n=4 WT) aged 6 weeks were examined with RSOM optoacoustic imaging systems (RSOM Explorer P50 at SWL 532nm and/or ms-P50 imaging system at 532 nm, 555 nm, 579 nm, and 606 nm). Images were reconstructed using a dedicated software, analyzed for size and vascular area and compared to standard histologic sections.ResultsRSOM enabled mapping of murine kidney size and vascular area, revealing differences between kidney sizes of male (m) and female (f) mice (merged frequencies (MF) f vs. m: 52.42±6.24 mm2 vs. 69.18±15.96 mm2, p=0.0156) and absolute vascular area (MF f vs. m: 35.67±4.22 mm2 vs. 49.07±13.48 mm2, p=0.0036). Without respect to sex, the absolute kidney area was found to be smaller in knock-out (KO) than in wildtype (WT) mice (WT vs. KO: MF: p=0.0255) and showed a similar trend for the relative vessel area (WT vs. KO: MF p=0.0031). Also the absolute vessel areas of KO compared to WT were found significantly different (MF p=0.0089). A significant decrease in absolute vessel area was found in KO compared to WT male mice (MF WT vs. KO: 54.37±9.35 mm2 vs. 34.93±13.82 mm2, p=0.0232). In addition, multispectral RSOM allowed visualization of oxygenated and deoxygenated parenchymal regions by spectral unmixing.ConclusionThis study demonstrates the capability of RSOM for label-free visualization of differences in vascular morphology in ex vivo murine renal tissue at high resolution. Due to its scalability optoacoustic imaging provides an emerging modality with potential for further preclinical and clinical imaging applications.

Pre-clinical evaluation of fretting-corrosion at stem-head and stem-cement interfaces of hip implants using in vitro and in silico models.

Prior to clinical use, the corrosion resistance of new prosthesis system must be verified. The fretting-corrosion mechanisms of total hip arthroplasty (THA) implants generate metal debris and ions that can increase the incidence of adverse tissue reactions. For cemented stems, there are at least two interfaces that can be damaged by fretting-corrosion: stem-head and stem-cement. This investigation aimed to evaluate, through in vitro and in silico analyses, fretting-corrosion at the stem-head and stem-cement interfaces, to determine which surface is most affected in pre-clinical testing and identify the causes associated with the observed behavior. Unimodular stems and femoral heads of three different groups were evaluated, defined according to the head/stem material as group I (SS/SS), group II (CoCr/SS), and group III (CoCr/CoCr). Seven pairs of stems and heads per group were tested: three pairs were subjected to material characterization, three pairs to in vitro fretting-corrosion testing, and one pair to geometric modeling in the in silico analysis. The absolute area of the stem body degraded was more than three times higher compared with the trunnion, for all groups. These results were corroborated by the in silico analysis results, which revealed that the average micromotion at the stem-cement interface (9.65-15.66 μm) was higher than that at the stem-head interface (0.55-1.08 μm). In conclusion, the degradation of the stem-cement interface is predominant in the pre-clinical set, indicating the need to consider the fretting-corrosion at the stem-cement interface during pre-clinical implant evaluations.

P78: Secukinumab treatment results in sustained improvement in absolute Psoriasis Area and Severity Index and Dermatological Life Quality Index in biologic‐naïve and biologic‐experienced patients with moderate‐to‐severe plaque psoriasis: analysis of 12 months of follow‐up data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

P78: Secukinumab treatment results in sustained improvement in absolute Psoriasis Area and Severity Index and Dermatological Life Quality Index in biologic‐naïve and biologic‐experienced patients with moderate‐to‐severe plaque psoriasis: analysis of 12 months of follow‐up data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

Itch as a critical factor in impaired health-related quality of life in patients with plaque psoriasis achieving clear or almost-clear skin: Analysis of the single-arm, open-label, multicenter, prospective ProLOGUE study

BackgroundPatients with psoriasis report impaired health-related quality of life (HRQoL; Dermatology Life Quality Index score ≥ 2) even after achieving clear or almost-clear skin with biologic treatment.ObjectiveTo assess the effectiveness of brodalumab in HRQoL improvement and the factors associated with incomplete HRQoL improvement in Japanese patients with psoriasis.MethodsAs a part of the single-arm, open-label, multicenter, prospective ProLOGUE study (Japan Registry of Clinical Trials identifier: jRCTs031180037), patients were treated with 210 mg of subcutaneous brodalumab in daily clinical practice until week 48. The absolute Psoriasis Area and Severity Index scores and patient-reported outcomes were assessed at baseline and weeks 12 and 48.ResultsSeventy-three patients (male, 82.2%; median age, 54.0 years) were enrolled. The Dermatology Life Quality Index and European Quality of Life 5-Dimension 5-Level Utility Index scores significantly improved from baseline to weeks 12 and 48. At week 48, all 13 patients with a Dermatology Life Quality Index score of ≥2 and an absolute Psoriasis Area and Severity Index score of 0 to ≤2 reported itching.LimitationsUnclear generalizability of the results to other biologics.ConclusionTreatment with brodalumab improved HRQoL in patients with psoriasis. Itching may contribute to incomplete HRQoL improvement in patients who have achieved clear or almost-clear skin.

Deep-Learning-Based Hemoglobin Concentration Prediction and Anemia Screening Using Ultra-Wide Field Fundus Images.

Background: Anemia is the most common hematological disorder. The purpose of this study was to establish and validate a deep-learning model to predict Hgb concentrations and screen anemia using ultra-wide-field (UWF) fundus images. Methods: The study was conducted at Peking Union Medical College Hospital. Optos color images taken between January 2017 and June 2021 were screened for building the dataset. ASModel_UWF using UWF images was developed. Mean absolute error (MAE) and area under the receiver operating characteristics curve (AUC) were used to evaluate its performance. Saliency maps were generated to make the visual explanation of the model. Results: ASModel_UWF acquired the MAE of the prediction task of 0.83 g/dl (95%CI: 0.81–0.85 g/dl) and the AUC of the screening task of 0.93 (95%CI: 0.92–0.95). Compared with other screening approaches, it achieved the best performance of AUC and sensitivity when the test dataset size was larger than 1000. The model tended to focus on the area around the optic disc, retinal vessels, and some regions located at the peripheral area of the retina, which were undetected by non-UWF imaging. Conclusion: The deep-learning model ASModel_UWF could both predict Hgb concentration and screen anemia in a non-invasive and accurate way with high efficiency.

Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Pedicel anatomy and histology in tomato vary according to genotype and water-deficit environment, affecting fruit mass

The growth and composition of fleshy fruits depend on resource acquisition and distribution in the plant. In tomato, the pedicel serves as the final connection between plant and fruit. However, very few quantitative data are available for the conducting tissues of the pedicel, nor is their genetic variability known. In the present study, a histological approach was combined with process-based modeling to evaluate the potential contribution made by the anatomy and histology of the pedicel to variations in fruit mass. Eleven genotypes were characterized and the impact of water deficit was studied for a single genotype using stress intensity and stage of application as variables. The results highlighted extensive variations in the relative proportions of the different pedicel tissues and in the absolute areas of xylem and phloem between genotypes. The model suggests that the variations in the area of the pedicel’s vascular tissues induced by differences in genotype and water-deficit environments partly contributed to fruit mass variability. They therefore warrant phenotyping for use in the development of plant strains adapted to future environmental constraints. The results also demonstrated the need to develop non-invasive in vivo measurement methods to establish the number and size of active vessels and the flow rates in these vessels to improve prediction of water fluxes in plant architecture.

Results of Structural and Bacteriological Analysis of the Mouse Adrenal Glands in a Sepsis Model.

The article presents the results of histological and bacteriological analysis of the adrenal glands in two models of sepsis caused by intraperitoneal administration of Pseudomonas aeruginosa strains 1623 and 5266 to sexually mature male C57BL/6 mice. In both models, histological changes in the adrenal glands in the dynamics of sepsis consist in cell destruction and decrease in the absolute areas of the zona glomerulosa, columnar part of the zona fasciculata, and medulla, the development of venous congestion in the absence of pronounced signs of leukocytic infiltration. Most adrenocortical cells of the zona glomerulosa and chromaffin cells of the medulla show signs of destruction. The columnar part of the zona fasciculata loses normal architectonics, the cells undergo degeneration and apoptosis, a significant part of cells in the deep layers of the zona fasciculata remain intact, but do not show tinctorial and ultrastructural signs of steroidogenesis. The active growth of P. aeruginosa colonies from adrenal homogenates in both models already in the first hours after infection of animals makes it possible to associate the revealed structural changes in the adrenal glands with the direct negative effect of P. aeruginosa, and high levels of mRNA of proinflammatory cytokines in the adrenal tissues raise the question of the possible synthesis of these modulators of inflammation in the adrenal parenchyma of septic animals.

Prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment: a nationwide study.

Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders). To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment. Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators. In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001). A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

Reliability of the passive leg movement assessment of vascular function in men.

What is the central question of this study? Use of the passive leg movement (PLM) test, a non-invasive assessment of microvascular function, is on the rise. However, PLM reliability in men has not been adequately investigated, nor has such reliability data, in men, been compared to the most commonly employed vascular function assessment, flow-mediated vasodilation (FMD). What is the main finding and its importance? PLM is a reliable method to assess vascular function in men, and is comparable to values previously reported for PLM in women, and for FMD. Given the importance of vascular function as a predictor of cardiovascular disease risk, these data support the utility of PLM as a clinically relevant measurement. Although vascular function is an independent predictor of cardiovascular disease risk, and therefore has significant prognostic value, there is currently not a single clinically accepted method of assessment. The passive leg movement (PLM) assessment predominantly reflects microvascular endothelium-dependent vasodilation and can identify decrements in vascular function with advancing age and pathology. Reliability of the PLM model was only recently determined in women, and has not been adequately investigated in men. Twenty healthy men (age: 27±2year) were studied on three separate experimental days, resulting in three within-day and three between-day trials. The hyperemic response to PLM was assessed with Doppler ultrasound, and expressed as the absolute peak in leg blood flow (LBFpeak ), change from baseline to peak (ΔLBFpeak ), absolute area under the curve (LBFAUC ), and change in AUC from baseline (ΔLBFAUC ). PLM-induced hyperemia yielded within-day coefficients of variation (CV) from 10.9 to 22.9%, intraclass correlation coefficients (ICC) from 0.82 to 0.90, standard error of the measurement (SEM) from 8.3 to 17.2%, and Pearson's correlation coefficients (r) from 0.56 to 0.81. Between-day assessments of PLM hyperemia resulted in CV from 14.4 to 25%, ICC from 0.75 to 0.87, SEM from 9.8 to 19.8%, and r from 0.46 to 0.75. Similar to previous reports in women, the hyperemic responses to PLM in men display moderate-to-high reliability, and are comparable to reliability data for brachial artery flow mediated vasodilation. These positive reliability findings further support the utility of PLM as a clinical measurement of vascular function and cardiovascular disease risk.

Mapping fire history and quantifying burned area through 35 years of prescribed fire history at an Illinois tallgrass prairie restoration site using GIS

Abstract Fire was important to pre‐colonization prairies. In today's remnant and reconstructed prairies, managers frequently employ prescribed fire, a historical management practice that limits woody encroachment, suppresses non‐native species and promotes nutrient cycling. However, few long‐term prescribed fire spatial datasets are available for study. We used archived images of prescribed fire maps and hand‐drawn fire records to generate a geospatial record of the prescribed fire history at Nachusa Grasslands, a combination remnant and restored preserve in northern Illinois. This record contains maps of the prescribed fire history of the preserve across the entirety of its 35‐year history. We used the maps to calculate both the absolute area and percentage of the preserve burned every year. This dataset compiles a long history of prescribed fire on a nature preserve and, due to the existing robust research programme at the preserve, can support the study of patterns in management applications of prescribed fire and examine the impacts of prescribed fire in restoration projects.

Modeling absolute zone size in retinopathy of prematurity in relation to axial length

Treatment outcomes in retinopathy of prematurity (ROP) are closely correlated with the location (i.e. zone) of disease, with more posterior zones having poorer outcomes. The most posterior zone, Zone I, is defined as a circle centered on the optic nerve with radius twice the distance from nerve to fovea, or subtending an angle of 30 degrees. Because the eye enlarges and undergoes refractive changes during the period of ROP screening, the absolute area of Zone I according to these definitions may likewise change. It is possible that these differences may confound accurate assessment of risk in patients with ROP. In this study, we estimated the area of Zone I in relation to different ocular parameters to determine how variability in the size and refractive power of the eye may affect zoning. Using Gaussian optics, a model was constructed to calculate the absolute area of Zone I as a function of corneal power, anterior chamber depth, lens power, lens thickness, and axial length (AL), with Zone I defined as a circle with radius set by a 30-degree visual angle. Our model predicted Zone I area to be most sensitive to changes in AL; for example, an increase of AL from 14.20 to 16.58 mm at postmenstrual age 32 weeks was calculated to expand the area of Zone I by up to 72%. These findings motivate several hypotheses which upon future testing may help optimize treatment decisions for ROP.

Long‐term, durable, absolute Psoriasis Area and Severity Index and health‐related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate‐to‐severe plaque psoriasis

BackgroundRisankizumab has demonstrated durable, high rates of efficacy in patients with moderate‐to‐severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1.ObjectivesThe aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health‐related quality of life (HRQoL) in patients with moderate‐to‐severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long‐term (>52 weeks to 172 weeks) risankizumab.MethodsData from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa‐1 and UltIMMa‐2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open‐label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1.ResultsSignificantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab‐treated patients compared with ustekinumab‐treated patients. Among patients treated with long‐term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment.ConclusionsRisankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.