Prospective assessment of inter-rater reliability of a neonatal adverse event severity scale

Introduction: To ensure the quality of clinical trial safety data, universal data standards are required. In 2019 the International Neonatal Consortium (INC) published a neonatal adverse event severity scale (NAESS) to standardize the reporting of adverse event (AE) severity. In this study the reliability of AE severity grading with INC NAESS was prospectively assessed in a real-world setting. Methods: Severity of AEs was assessed by two independent observers at each of four centers across the world. In each center two series of 30 neonatal adverse events were assessed by both observers: in a first phase with a generic (Common Terminology Criteria for Adverse Events, CTCAE) severity scale not specific to neonates, and in a second phase with INC NAESS (after a structured training). Intraclass correlation coefficients (ICC) were calculated to express inter-rater agreement in both phases, and bootstrap sampling was used to compare them. Results: 120 AEs were included in each of both phases. The ICC with the use of INC NAESS in phase 2 was 0.69. This represents a significant but modest improvement in comparison to the initial ICC of 0.66 in phase 1 (confidence interval of ratio of ICC in phase 2 to phase 1 = 1.005–1.146; excludes 1). The ICC was higher for those AEs for which a diagnosis specific AE severity table was available in INC NAESS (ICC 0.80). Discussion: Good inter-rater reliability of the INC NAESS was demonstrated in four neonatal intensive care units (NICUs) across the globe. The ICC is comparable to what is reported for scales with similar purposes in different populations. There is a modest, but significant, improvement in inter-rater agreement in comparison to the naïve phase without INC NAESS. The better performance when reviewers use AE-specific NAESS tables highlights the need to expand the number of AEs that are covered by specific criteria in the current version of INC NAESS.</p

“A Cathartic Moment in a Man’s Life”: Homosociality and Gendered Fun on the Puttan Tour

Rarely addressed in academic scholarship, the puttan tour is a well-known form of entertainment in Italy where young men drive around in small groups with the aim of spotting street sex workers. On some occasions, the participants will approach the sex workers to strike up a conversation. On others, they will shout out insults from their car then drive away. This article aims to advance a detailed analysis of this underexplored cultural practice drawing on a diverse body of scholarship exploring the intersection of masculinity, leisure, and homosociality. By analyzing stories of puttan tours gathered mostly online, including written accounts and YouTube videos, our aim is to explore the appeal of the puttan tour through an analysis of how homosociality, humor, and laughter operate in this example of gendered fun. To this end, we look at the multiple and often equivocal meanings of this homosocial male-bonding ritual, its emotional and affective dynamics, and the ways in which it reproduces structures of inequality while normalizing violence against sex workers

Adjuvanted Fusion Protein Vaccine Induces Durable Immunity to Onchocerca volvulus in Mice and Non-Human Primates

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with Ov-FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that Ov-FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against O. volvulus in mice and NHPs that is mediated by vaccine-induced humoral factors

Adjuvanted Fusion Protein Vaccine Induces Durable Immunity to Onchocerca volvulus in Mice and Non-Human Primates

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with Ov-FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that Ov-FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against O. volvulus in mice and NHPs that is mediated by vaccine-induced humoral factors.</jats:p

One health, une seule santé

One Health, « Une seule santé », est une stratégie mondiale visant à développer les collaborations interdisciplinaires pour la santé humaine, animale et environnementale. Elle promeut une approche intégrée, systémique et unifiée de la santé aux échelles locale, nationale et mondiale, afin de mieux affronter les maladies émergentes à risque pandémique, mais aussi s'adapter aux impacts environnementaux présents et futurs. Bien que ce mouvement s’étende, la littérature en français reste rare. Traduit de l’anglais, coordonné par d’éminents épidémiologistes et s'appuyant sur un large panel d' approches scientifiques rarement réunies autour de la santé, cet ouvrage retrace les origines du concept et présente un contenu pratique sur les outils méthodologiques, la collecte de données, les techniques de surveillance et les plans d’étude. Il combine recherche et pratique en un seul volume et constitue un ouvrage de référence unique pour la santé mondiale

Structure-based Design of JOC-x, a Conjugatable Tumor Tight Junction Opener to Enhance Cancer Therapy

Abstract Disorganized intercellular junctions are critical for maintaining the integrity of solid epithelial tumors and prevent the infiltration of oncological therapies into the bulk of the malignancy. We have developed small, recombinant proteins which bind a critical junction protein, desmoglein 2, triggering the transient and specific opening of tumor tight junctions allowing for infiltration of the tumor with immune cells, oncolytic viruses, drugs, and other therapeutics. Our new molecule, JOC-x, is a promising candidate for a new class of tumor-targeting agents that accumulate both around and within tumors and remodel the tumor microenvironment. Native cysteines were removed from the parental protein, JO-4, followed by addition of a single cysteine to allow for convenient attachment of various payloads that can be targeted directly to the tumor. Our tumor-targeting protein exhibits high avidity, minimal aggregation, and is easily purified at good yields from E. coli. For proof of concept, we demonstrate effective conjugation to biotin as a model for flexible co-targeting, addition of metal ion chelators as models for imaging and radiotherapy, and linkage of the TLR3 agonist poly(I:C) as a model immune-oncologic agent. This second-generation cancer co-therapeutic protein is optimized for activity and primed for cGMP manufacture in preparation for upcoming clinical studies

Pre-clinical development of a vaccine for human lymphatic filariasis

This study was conducted to optimize a fusion protein vaccine for translational development as a vaccine against the human tropical parasitic infection, lymphatic filariasis (LF). The vaccine candidate, His-tagged rBmHAXT was developed previously in our laboratory and was tested in various animal models including mouse, gerbils and Rhesus macaque where it exhibited significant levels of vaccine-induced protection. However, for commercial manufacturing and for regulatory approval for human use, there was a need to modify the vaccine antigen and its production and analytical release methods. Therefore, the major focus of this study was to develop a process for manufacturing an affinity tag-free rBmHAXT and evaluate its immunogenicity, potency and protective efficacy in both inbred and outbred mouse models, as well as in outbred gerbil models. Our results demonstrate that the tag-free rBmHAXT vaccine produced with a process suitable for cGMP production had protective properties equivalent to the original His-tagged rBmHAXT

An analysis of training, generalization, and maintenance effects of Primary Care Triple P for parents of preschool-aged children with disruptive behavior

A brief primary care intervention for parents of preschool-aged children with disruptive behavior was assessed using a multiple probe design. Primary Care Triple P, a four session behavioral intervention was sequentially introduced within a multiple probe format to each of 9 families to a total of 10 children aged between 3 and 7 years (males = 4, females = 6). Independent observations of parent-child interaction in the home revealed that the intervention was associated with lower levels of child disruptive behavior both in a target training setting and in various generalization settings. Parent report data also confirmed there were significant reductions in intensity and frequency of disruptive behavior, an increase in task specific parental self-efficacy, improved scores on the Parent Experience Survey, and high levels of consumer satisfaction. All short-term intervention effects were maintained at four-month follow-up. Implications for the delivery of brief interventions to prevent conduct problems are discussed