Comparative safety and benefit-risk profile of biologics and oral treatment for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data

Background The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. Objective To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. Methods A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). Results Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. Limitations The results may not be generalizable to real-world populations. Conclusions Anti–interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term

Einstein equations in the null quasi-spherical gauge

The structure of the full Einstein equations in a coordinate gauge based on expanding null hypersurfaces foliated by metric 2-spheres is explored. The simple form of the resulting equations has many applications -- in the present paper we describe the structure of timelike boundary conditions; the matching problem across null hypersurfaces; and the propagation of gravitational shocks.Comment: 12 pages, LaTeX (revtex, amssymb), revision 18 pages, contains expanded discussion and explanations, updated references, to appear in CQ

Ordinal-Level Phylogenomics of the Arthropod Class Diplopoda (Millipedes) Based on an Analysis of 221 Nuclear Protein-Coding Loci Generated Using Next-Generation Sequence Analyses

Background The ancient and diverse, yet understudied arthropod class Diplopoda, the millipedes, has a muddled taxonomic history. Despite having a cosmopolitan distribution and a number of unique and interesting characteristics, the group has received relatively little attention; interest in millipede systematics is low compared to taxa of comparable diversity. The existing classification of the group comprises 16 orders. Past attempts to reconstruct millipede phylogenies have suffered from a paucity of characters and included too few taxa to confidently resolve relationships and make formal nomenclatural changes. Herein, we reconstruct an ordinal-level phylogeny for the class Diplopoda using the largest character set ever assembled for the group. Methods Transcriptomic sequences were obtained from exemplar taxa representing much of the diversity of millipede orders using second-generation (i.e., next-generation or high-throughput) sequencing. These data were subject to rigorous orthology selection and phylogenetic dataset optimization and then used to reconstruct phylogenies employing Bayesian inference and maximum likelihood optimality criteria. Ancestral reconstructions of sperm transfer appendage development (gonopods), presence of lateral defense secretion pores (ozopores), and presence of spinnerets were considered. The timings of major millipede lineage divergence points were estimated. Results The resulting phylogeny differed from the existing classifications in a number of fundamental ways. Our phylogeny includes a grouping that has never been described (Juliformia+Merocheta+Stemmiulida), and the ancestral reconstructions suggest caution with respect to using spinnerets as a unifying characteristic for the Nematophora. Our results are shown to have significantly stronger support than previous hypotheses given our data. Our efforts represent the first step toward obtaining a well-supported and robust phylogeny of the Diplopoda that can be used to answer many questions concerning the evolution of this ancient and diverse animal group

Terrestrial arachnids

74 p. : ill. ; 26 cm.Includes bibliographical references (p. 72-74)."Three new genera and seven new species of the arachnid order Trigonotarbida are described based on remarkably well preserved fossils from the late Middle Devonian (Givetian) of Gilboa, New York: Gilboarachne griersoni, Gelasinotarbus reticulatus, G. bonamoae, G. bifidus, G. heptops, G.? fimbriunguis, and Aculeatarbus depressus. A brief review of other known Devonian trigonotarbids is presented, and certain misconceptions about the order are rectified, including the nature of the eyes, chelicerae, claws, and abdominal segmentation. Trigonotarbida is shown by cladistic analysis to be the plesiomorphic sister-group of Araneae + Amblypygi + Uropygi + Schizomida"--P. 2

A population study comparing screening performance of prototypes for depression and anxiety with standard scales

<p>Abstract</p> <p>Background</p> <p>Screening instruments for mental disorders need to be short, engaging, and valid. Current screening instruments are usually questionnaire-based and may be opaque to the user. A prototype approach where individuals identify with a description of an individual with typical symptoms of depression, anxiety, social phobia or panic may be a shorter, faster and more acceptable method for screening. The aim of the study was to evaluate the accuracy of four new prototype screeners for predicting depression and anxiety disorders and to compare their performance with existing scales.</p> <p>Methods</p> <p>Short and ultra-short prototypes were developed for Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), Panic Disorder (PD) and Social Phobia (SP). Prototypes were compared to typical short and ultra-short self-report screening scales, such as the Centre for Epidemiology Scale, CES-D and the GAD-7, and their short forms. The Mini International Neuropsychiatric Interview (MINI) version 6 <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> was used as the gold standard for obtaining clinical criteria through a telephone interview. From a population sample, 225 individuals who endorsed a prototype and 101 who did not were administered the MINI. Receiver operating characteristic (ROC) curves were plotted for the short and ultra short prototypes and for the short and ultra short screening scales.</p> <p>Results</p> <p>The study found that the rates of endorsement of the prototypes were commensurate with prevalence estimates. The short-form and ultra short scales outperformed the short and ultra short prototypes for every disorder except GAD, where the GAD prototype outperformed the GAD 7.</p> <p>Conclusions</p> <p>The findings suggest that people may be able to self-identify generalised anxiety more accurately than depression based on a description of a prototypical case. However, levels of identification were lower than expected. Considerable benefits from this method of screening may ensue if our prototypes can be improved for Major Depressive Disorder, Social Phobia and Panic Disorder.</p

The evolution of prey‐wrapping behaviour in spiders

We traced the evolution of silk use by spiders in attacks on prey by combining previous publications with new observations of 31 species in 16 families. Two new prey‐wrapping techniques are described. One, in which the spider holds a tense line (often covered with viscid silk) with both legs IV and applies it to the prey with a simultaneous movement of both legs, may be a synapomorphy linking Theridiidae, Nesticidae, and Synotaxidae. The other, in which the spider stands over the prey and turns in place, is apparently very ancient; it occurs in Theraphosidae, Tengellidae, and Agelenidae. The use of legs IV to wrap prey is described for the first time in Filistatidae and Scytodidae. Using a recent phylogeny of spiders, we propose that prey wrapping with legs IV has evolved convergently at least four times. We propose that prey wrapping originally evolved from egg‐sac construction behaviour.Instituto Smithsoniano de Investigaciones Tropicales (STRI)Universidad de Costa RicaUCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biologí

Congenital Plasmodium falciparum infection in neonates in Muheza District, Tanzania

BACKGROUND\ud \ud Although recent reports on congenital malaria suggest that the incidence is increasing, it is difficult to determine whether the clinical disease is due to parasites acquired before delivery or as a result of contamination by maternal blood at birth. Understanding of the method of parasite acquisition is important for estimating the time incidence of congenital malaria and design of preventive measures. The aim of this study was to determine whether the first Plasmodium falciparum malaria disease in infants is due to same parasites present on the placenta at birth.\ud \ud METHODS\ud \ud Babies born to mothers with P. falciparum parasites on the placenta detected by PCR were followed up to two years and observed for malaria episodes. Paired placental and infant peripheral blood samples at first malaria episode within first three months of life were genotyped (msp2) to determine genetic relatedness. Selected amplifications from nested PCR were sequenced and compared between pairs.\ud \ud RESULTS\ud \ud Eighteen (19.1%) out of 95 infants who were followed up developed clinical malaria within the first three months of age. Eight pairs (60%) out of 14 pairs of sequenced placental and cord samples were genetically related while six (40%) were genetically unrelated. One pair (14.3%) out of seven pairs of sequenced placental and infants samples were genetically related. In addition, infants born from primigravidae mothers were more likely to be infected with P. falciparum (P < 0.001) as compared to infants from secundigravidae and multigravidae mothers during the two years of follow up. Infants from multigravidae mothers got the first P. falciparum infection earlier than those from secundigravidae and primigravidae mothers (RR = 1.43).\ud \ud CONCLUSION\ud \ud Plasmodium falciparum malaria parasites present on the placenta as detected by PCR are more likely to result in clinical disease (congenital malaria) in the infant during the first three months of life. However, sequencing data seem to question the validity of this likelihood. Therefore, the relationship between placental parasites and first clinical disease need to be confirmed in larger studies

High blood pressure in school children: prevalence and risk factors

BACKGROUND: The purpose of this study was to determine the prevalence of high blood pressure (HBP) and associated risk factors in school children 8 to 13 years of age. METHODS: Elementary school children (n = 1,066) were examined. Associations between HBP, body mass index (BMI), gender, ethnicity, and acanthosis nigricans (AN) were investigated using a school based cross-sectional study. Blood pressure was measured and the 95(th )percentile was used to determine HBP. Comparisons between children with and without HBP were utilized. The crude and multiple logistic regression adjusted odds ratios were used as measures of association. RESULTS: Females, Hispanics, overweight children, and children with AN had an increased likelihood of HBP. Overweight children (BMI ≥ 85(th )percentile) and those with AN were at least twice as likely to present with HBP after controlling for confounding factors. CONCLUSION: Twenty one percent of school children had HBP, especially the prevalence was higher among the overweight and Hispanic group. The association identified here can be used as independent markers for increased likelihood of HBP in children

Furfural uptake by Neurospora ascospores

Furfural uptake was studied with regard to possible mechanisms of inducing germination in ascospores. Uptake was found to involve a large, weakly bound reversible component and a small tightly bound irreversible component. Localization experiments indicate that almost all of the furfural removed from the media is bound to the spore wall. However, a small amount may penetrate into the cytoplasm. The results so far suggest that furfural induces germination by solubilizing or activating a bound or compartmentalized enzyme(s) on the cell membrane or other diffusion barrier of the cell.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47494/1/425_2004_Article_BF00385758.pd

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC