Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

BACKGROUND: Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. OBJECTIVE: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. METHODS: In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. RESULTS: Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. CONCLUSIONS: Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

Bayesian analysis for partly linear Cox model with measurement error and time-varying covariate effect.

The Cox proportional hazards model is commonly used to estimate the association between time-to-event and covariates. Under the proportional hazards assumption, covariate effects are assumed to be constant in the follow-up period of study. When measurement error presents, common estimation methods that adjust for an error-contaminated covariate in the Cox proportional hazards model assume that the true function on the covariate is parametric and specified. We consider a semiparametric partly linear Cox model that allows the hazard to depend on an unspecified function of an error-contaminated covariate and an error-free covariate with time-varying effect, which simultaneously relaxes the assumption on the functional form of the error-contaminated covariate and allows for nonconstant effect of the error-free covariate. We take a Bayesian approach and approximate the unspecified function by a B-spline. Simulation studies are conducted to assess the finite sample performance of the proposed approach. The results demonstrate that our proposed method has favorable statistical performance. The proposed method is also illustrated by an application to data from the AIDS Clinical Trials Group Protocol 175.

PSegNet: Simultaneous Semantic and Instance Segmentation for Point Clouds of Plants.

Phenotyping of plant growth improves the understanding of complex genetic traits and eventually expedites the development of modern breeding and intelligent agriculture. In phenotyping, segmentation of 3D point clouds of plant organs such as leaves and stems contributes to automatic growth monitoring and reflects the extent of stress received by the plant. In this work, we first proposed the Voxelized Farthest Point Sampling (VFPS), a novel point cloud downsampling strategy, to prepare our plant dataset for training of deep neural networks. Then, a deep learning network-PSegNet, was specially designed for segmenting point clouds of several species of plants. The effectiveness of PSegNet originates from three new modules including the Double-Neighborhood Feature Extraction Block (DNFEB), the Double-Granularity Feature Fusion Module (DGFFM), and the Attention Module (AM). After training on the plant dataset prepared with VFPS, the network can simultaneously realize the semantic segmentation and the leaf instance segmentation for three plant species. Comparing to several mainstream networks such as PointNet++, ASIS, SGPN, and PlantNet, the PSegNet obtained the best segmentation results quantitatively and qualitatively. In semantic segmentation, PSegNet achieved 95.23%, 93.85%, 94.52%, and 89.90% for the mean Prec, Rec, F1, and IoU, respectively. In instance segmentation, PSegNet achieved 88.13%, 79.28%, 83.35%, and 89.54% for the mPrec, mRec, mCov, and mWCov, respectively.

A switching event-triggered resilient control scheme for primary and secondary levels in AC microgrids.

In microgrid hierarchical control, primary control to stabilize system and secondary control to eliminate frequency/voltage deviations are both necessary for islanded microgrids. In this paper, a switching event-triggered (SET) resilient control scheme for microgrid primary and secondary levels has been proposed. First, droop control and model predictive control (MPC) are used for power sharing and driving signal generation respectively on primary level. An SET control method to trigger different MPC cost functions is proposed to balance output voltage quality and switching frequency. Then, distributed consensus and pinning control based method is used on secondary level. An SET mechanism to dynamically adjust secondary ratios to coordinate the transient deviation and response speed is proposed. Next, to deal with severe accidents, a resilient control scheme integrating primary and secondary levels is designed to maintain the system sound operation and improve the system immunity. Finally, the effectiveness of the proposed control scheme has been demonstrated by simulation with comprehensive scenarios.

Effectiveness of neuraminidase inhibitors to prevent mortality in patients with laboratory-confirmed avian influenza A H7N9.

OBJECTIVES: Avian influenza virus A(H7N9) remains a threat to humans and has great potential to cause a pandemic in the foreseeable future. Antiviral treatment with neuraminidase inhibitors has been recommended to treat patients with H7N9 infection as early as possible, although evidence-based research on their effectiveness for H7N9 infection is lacking. METHODS: Data from all laboratory-confirmed cases of H7N9 infection in Zhejiang Province between 2013 and 2017 were retrieved, and time-dependent survival models were used to evaluate the effectiveness of treatment with neuraminidase inhibitors to reduce the risk of mortality. RESULTS: The final optimal model found no significant association (odds ratio 1.29, 95% confidence interval 0.78-2.15) between time to treatment with neuraminidase inhibitors and survival after controlling for age and white blood cell count. Sensitivity analyses with multiple imputation for missing data concurred with the primary analysis. CONCLUSIONS: No association was found between treatment with neuraminidase inhibitors and survival in patients with H7N9 infection using various adjusted models and sensitivity analyses of missing data imputations.

Reaction Force Mapping by 3-Axis Tactile Sensing With Arbitrary Angles for Tissue Hard-Inclusion Localization.

Although robot-assisted diagnosis and minimally invasive surgery (MIS) brings distinct benefits, deficient multi-dimensional force feedback remains a noteworthy limitation and challenge in MIS. Aiming for a comprehensive high-fidelity perception of tissue-instrument interactions, we present a Fiber Bragg Grating (FBG)-based 3-axis tactile sensing for surface reaction force mapping, identification and localization of tissue hard-inclusion. The tactile sensing probe consists of five optical fibers inscribed with FBGs and a force-sensitive 3D printed deformable body. All fibers are suspended inside the deformable body in a parallel manner, leading to the direct compression or tension of each FBG. Such configuration can effectively avoid the chirping failure of FBG compared with the pasting FBG-based sensors. A linearized difference model is proposed to calibrate the 3-axis force detection and enhance the resistance to nonlinear interferences. Hard-inclusion identification experiments with varied hard-inclusion sizes and depths have been implemented through discrete palpation and dragging palpation modes. Results indicate that the probe can effectively identify the presence and location of these small hard-inclusions from the force mapping. Furthermore, lengthy vessels embedded in the phantom can be accurately identified through dragging palpation with an arbitrary contact angle. Another novelty of the probe is the reconstruction of the surface profile of a non-planar tissue, which further allows hard-inclusion identification and 3D localization. Ex-vivo tissue palpation on a porcine kidney further validates the effectiveness and feasibility of the probe to map surface reaction forces and localize the hard-inclusions intraoperatively.

Time-series analysis of satellite-derived fine particulate matter pollution and asthma morbidity in Jackson, MS.

In order to examine associations between asthma morbidity and local ambient air pollution in an area with relatively low levels of pollution, we conducted a time-series analysis of asthma hospital admissions and fine particulate matter pollution (PM2.5) in and around Jackson, MS, for the period 2003 to 2011. Daily patient-level records were obtained from the Mississippi State Department of Health (MSDH) Asthma Surveillance System. Patient geolocations were aggregated into a grid with 0.1° × 0.1° resolution within the Jackson Metropolitan Statistical Area. Daily PM2.5 concentrations were estimated via machine-learning algorithms with remotely sensed aerosol optical depth and other associated parameters as inputs. Controlling for long-term temporal trends and meteorology, we estimated a 7.2% (95% confidence interval 1.7-13.1%) increase in daily all-age asthma emergency room admissions per 10 µg/m3 increase in the 3-day average of PM2.5 levels (current day and two prior days). Stratified analyses reveal significant associations between asthma and 3-day average PM2.5 for males and blacks. Our results contribute to the current epidemiologic evidence on the association between acute ambient air pollution exposure and asthma morbidity, even in an area characterized by relatively good air quality.

Time-Series Analysis of Air Pollution and Health Accounting for Covariate-Dependent Overdispersion.

Time-series studies are routinely used to estimate associations between adverse health outcomes and short-term exposures to ambient air pollutants. Use of the Poisson log-linear model with the assumption of constant overdispersion is the most common approach, particularly when estimating associations between daily air pollution concentrations and aggregated counts of adverse health events throughout a geographical region. We examined how the assumption of constant overdispersion plays a role in estimation of air pollution effects by comparing estimates derived from the standard approach with those estimated from covariate-dependent Bayesian generalized Poisson and negative binomial models that accounted for potential time-varying overdispersion. Through simulation studies, we found that while there was negligible bias in effect estimates, the standard quasi-Poisson approach can result in a larger standard error when the constant overdispersion assumption is violated. This was also observed in a time-series study of daily emergency department visits for respiratory diseases and ozone concentration in Atlanta, Georgia (1999-2009). Allowing for covariate-dependent overdispersion resulted in a reduction in the ozone effect standard error, while the ozone-associated relative risk remained robust to different model specifications. Our findings suggest that improved characterization of overdispersion in time-series modeling can result in more precise health effect estimates in studies of short-term environmental exposures.

Mucosal Healing in Clinical Practice: A Single-Center Pediatric IBD Experience.

BACKGROUND: Mucosal healing (MH) is associated with improved clinical outcomes in patients with Crohn's disease (CD) and ulcerative colitis (UC). MH as a target for treatment has been suggested, although there is little pediatric data. The goal of this study was to evaluate MH in clinical practice in pediatric patients with inflammatory bowel disease in clinical remission. METHODS: A retrospective review of electronic health record data was performed on all patients with CD or UC who underwent at least 2 colonoscopies from 2010 through 2016. Only patients in clinical remission undergoing a scope for MH were included in our study. The incidence of MH and histologic healing (HH) was analyzed, along with cumulative rates of MH in each group. MH was defined by both physician assessment of MH and an endoscopic score of zero for CD and UC. RESULTS: A total of 76 patients with CD and 28 patients with UC underwent at least one MH scope while in clinical remission. Of the 76 patients with CD, 51 patients (67%) demonstrated MH by physician assessment, 34 patients (45%) demonstrated MH by a simple endoscopic score for CD of zero, and 35 patients (46%) demonstrated HH. Of the 28 patients with UC, 20 patients (71%) demonstrated MH by physician assessment, 10 patients (36%) demonstrated MH by a Mayo score of zero, and 10 patients (36%) demonstrated HH. Nineteen patients underwent a second MH scope and 11 (58%) demonstrated MH by physician assessment, 7 patients (37%) demonstrated MH by simple endoscopic score for CD or Mayo scores of zero, and 5 patients (26%) demonstrated HH. Of those patients with active disease, 21 of 25 patients with CD underwent escalation of therapy, whereas 8 of 8 patients with UC underwent escalation of therapy. Cumulative rates of MH when defined by physician assessment were 79% (60 of 76 patients) in CD and 79% (22 of 28 patients) in UC. CONCLUSIONS: MH is feasible in pediatric CD and UC, and rates of cumulative MH in pediatric patients are similar to previously published adult data. In children with inflammatory bowel disease in clinical remission, approximately one-third demonstrate active disease at endoscopy.

Pediatric injury prevention programs: Identifying markers for success and sustainability.

BACKGROUND: Injury is the leading cause of death in children. Although many pediatric hospitals and trauma centers provide injury prevention (IP) programming, there is no national standard. This study aims to identify characteristics of a sustainable and successful IP program by querying programs affiliated with the Injury Free Coalition for Kids (IFCK). METHODS: The IFCK sites were sent a 30-question survey via e-mail. Questions focused on demographics, scope of IP activities, self-efficacy, and outcome measures including finances, academic productivity, and legislative advocacy. Counts and frequencies were calculated and compared using χ tests. RESULTS: The survey was completed by 38 (90.4%) of 42 sites. The majority were associated with a freestanding children's hospital (57.9%) and Level I pediatric trauma center (86.8%). Most programs (79%) had at least one dedicated full-time equivalent (FTE) staff. Research was most common on child passenger safety and teen driving. Nearly 30% of programs offered educational curricula to health care providers; these sites were more likely to have FTE support (p = 0.036). Steady sources of funding were identified for 60.5% of programs, with 47.8% citing their hospital as the primary source; 73% of respondents were confident in their program's capacity to sustain activities; these were more likely to be larger programs (p = 0.001) with steady sources of funding (p < 0.001). Despite 73.7% of sites having academic affiliations, 60.5% had 5 or fewer publications over the previous 5 years. In the prior 2 years, 55.3% of programs impacted legislative or policy changes. Funding, size of program, and FTE had no statistical correlation with research productivity or number of legislative/policy contributions. CONCLUSIONS: This study characterizes the variation among pediatric IP programs within IFCK sites, while highlighting the association between financial and FTE support from programs' institutions with sustainable IP programming. These results can assist programs in identifying differences in relation to their peers.

The Relationship Between Zinc and Quality of Life in Patients With Upper GI Cancer on Chemotherapy.

This is a pilot study aimed at evaluating the prevalence of zinc deficiency and how zinc levels affect the quality of life (QOL) of patients with upper gastrointestinal (GI) cancers receiving systemic chemotherapy. The data collection was completed on 40 patients. Although the primary objective of a positive prevalence of zinc deficiency in upper GI cancer patients at diagnosis and after receiving chemotherapy is not statistically significant, we found a statistically significant association between zinc level and certain QOL factors. There is a significantly positive association with satisfaction of social contact at baseline only, sexual pleasure at baseline and at 2 months, QOL at baseline only, and troublesome sweating at baseline, and from baseline to 2 months corresponding with change in other skin problems. Conversely, there is a significantly negative association corresponding changes in enjoyment of physical activities, how the patient usually feels, sexual pleasure, the way in which the patient approaches food, QOL, rashes on the face, and other skin problems. Neutropenia grades were reflective of decreased zinc at baseline but did not show decreased zinc correlating with a weakened immune system.

Evaluation of real-time loop-mediated isothermal amplification (RealAmp) for rapid detection of Mycobacterium tuberculosis from sputum samples.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) leads to serious health problems as a chronic respiratory infectious disease. Here we established a real-time fluorescence loop-mediated isothermal amplification assay (RealAmp) using a portable ESE Quant tube scanner as a convenient rapid detection method for MTB. The method efficacy from sputum samples was further investigated, and the reaction time was only 20min with the detection limit low to 10(2)CFU/ml concentration of MTB. We assessed a total of 1067 samples by the RealAmp assay, comparing the results with smear microscopy and conventional culture methods. To examine whether the failure to detect TB by culturing is due to low sensitivity or true absence, we examined the culture negative samples by commercial real time PCR MTB detection kit, and the results were compared with RealAmp. The data showed that RealAmp assay had a higher positive rate than that of sputum smear and culture methods. RealAmp had a sensitivity of 96.70% and a specificity of 91.55% when compared with culture. In addition, its sensitivity and specificity were 95.29% and 86.88% respectively compared with examination of smear samples using light microscopy. The sensitivity of RealAmp in comparison to real time PCR was 98.25% and specificity was 99.11% in validation of culture negative samples. The present study revealed the newly established RealAmp assay as a convenient, efficient, sensitive and specific method that could be an alternative for rapid detection of MTB and a tool to validate culture and smear negative samples. Furthermore, the portability of the ESE Quant tube scanner also contributed to the promising application for grassroots and field detection of MTB.