Forty years of temporal analysis of products

A detailed understanding of reaction mechanisms and kinetics is required in order to develop and optimize catalysts and catalytic processes. While steady-state investigations are known to give a global view of the catalytic system, transient studies are invaluable since they can provide more comprehensive insight into elementary steps. For almost forty years temporal analysis of products (TAP) has been successfully utilized for transient studies of gas phase heterogeneous reactions, and there have been a number of advances in instrumentation and numerical modeling methods in that time. Since TAP is a complex methodology it is often viewed as a niche specialty. With the purpose to make TAP more relevant and approachable to a wider segment of the catalytic research community, part of the intention of this work is to highlight the significant contributions TAP has made to elucidating mechanistic and kinetic aspects of complex, multi-step heterogeneous reactions. With this in mind, an outlook is also disclosed for the technique in terms of what is needed to revitalize the field and make it more applicable to the recent advances in catalyst characterization (e.g. operando modes)

Identification of Natural Bispecific Antibodies against Cyclic Citrullinated Peptide and Immunoglobulin G in Rheumatoid Arthritis

BACKGROUND: Previous studies indicate that natural bispecific antibodies can be readily produced in vivo when the body is simultaneously stimulated with 2 distinct antigens. Patients with rheumatoid arthritis (RA) usually exhibit persistent immune responses to various autoantigens, raising the possibility that natural bispecific antibodies against 2 distinct autoantigens might exist. METHODOLOGY/PRINCIPAL FINDINGS: We identified the presence of natural bispecific antibodies against cyclic citrullinated peptide (CCP) and immunoglobulin G (IgG) in RA patients' sera by means of a double-antigen sandwich enzyme-linked immunosorbent assay (ELISA). The spontaneous emergence of bispecific antibodies was confirmed by mixing different proportions of 1 anti-CCP-positive serum and 1 rheumatoid factor (RF)-positive serum in vitro. Among the tested samples, positive correlations were found between the presence of bispecific antibodies and both IgG4 anti-CCP antibodies and IgG4 RF (r = 0.507, p<0.001 and r = 0.249, p = 0.044, respectively), suggesting that the IgG4 subclass is associated with this phenomenon. Furthermore, bispecific antibodies were selectively generated when several anti-CCP- and RF-positive sera were mixed pairwise, indicating that factors other than the monospecific antibody titers may also contribute to the production of the natural bispecific antibodies. CONCLUSIONS/SIGNIFICANCE: We successfully identified the presence of natural bispecific antibodies. Our results suggest that these antibodies originate from anti-CCP and RF in the sera of RA patients. The natural occurrence of bispecific antibodies in human diseases may provide new insights for a better understanding of the diseases. Further investigations are needed to elucidate their precise generation mechanisms and explore their clinical significance in disease development and progression in a larger study population

Molecular epidemiology of serogroup a meningitis in Moscow, 1969 to 1997.

Molecular analysis of 103 serogroup A Neisseria meningitidis strains isolated in Moscow from 1969 to 1997 showed that four independent clonal groupings were responsible for successive waves of meningococcal disease. An epidemic from 1969 to the mid-1970s was caused by genocloud 2 of subgroup III, possibly imported from China. Subsequent endemic disease through the early 1990s was caused by subgroup X and then by subgroup VI, which has also caused endemic disease elsewhere in eastern Europe. A 1996 epidemic was part of the pandemic spread from Asia of genocloud 8 of subgroup III. Recent genocloud 8 epidemic disease in Moscow may represent an early warning for spread of these bacteria to other countries in Europe

Pedestrian Injury and Human Behaviour: Observing Road-Rule Violations at High-Incident Intersections

Background Human behaviour is an obvious, yet under-studied factor in pedestrian injury. Behavioural interventions that address rule violations by pedestrians and motorists could potentially reduce the frequency of pedestrian injury. In this study, a method was developed to examine road-rule non-compliance by pedestrians and motorists. The purpose of the study was to examine the potential association between violations made by pedestrians and motorists at signalized intersections, and collisions between pedestrians and motor-vehicles. The underlying hypothesis is that high-incident pedestrian intersections are likely to vary with respect to their aetiology, and thus are likely to require individualized interventions – based on the type and rate of pedestrian and motorist violation. Methods High-incident pedestrian injury intersections in Vancouver, Canada were identified using geographic information systems. Road-rule violations by pedestrians and motorists were documented at each incident hotspot by a team of observers at several different time periods during the day. Results Approximately 9,000 pedestrians and 18,000 vehicles were observed in total. In total for all observed intersections, over 2000 (21%) pedestrians committed one of the observed pedestrian road-crossing violations, while approximately 1000 (5.9%) drivers committed one of the observed motorist violations. Great variability in road-rule violations was observed between intersections, and also within intersections at different observation periods. Conclusions Both motorists and pedestrians were frequently observed committing road-rule violations at signalized intersections, suggesting a potential human behavioural contribution to pedestrian injury at the study sites. These results suggest that each intersection may have unique mechanisms that contribute to pedestrian injury, and may require targeted behavioural interventions. The method described in this study provides the basis for understanding the relationship between violations and pedestrian injury risk at urban intersections. Findings could be applied to targeted prevention campaigns designed to reduce the number of pedestrian injuries at signalized intersections

Real-time conformational changes and controlled orientation of native proteins inside a protein nanoreactor

Protein conformations play crucial roles in most, if not all, biological processes. Here we show that the current carried through a nanopore by ions allows monitoring conformational changes of single and native substrate-binding domains (SBD) of an ATP-Binding Cassette importer in real-time. Comparison with single-molecule Förster Resonance Energy Transfer and ensemble measurements revealed that proteins trapped inside the nanopore have bulk-like properties. Two ligand-free and two ligand-bound conformations of SBD proteins were inferred and their kinetic constants were determined. Remarkably, internalized proteins aligned with the applied voltage bias, and their orientation could be controlled by the addition of a single charge to the protein surface. Nanopores can thus be used to immobilize proteins on a surface with a specific orientation, and will be employed as nanoreactors for single-molecule studies of native proteins. Moreover, nanopores with internal protein adaptors might find further practical applications in multianalyte sensing devices

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Incidence of unplanned excisions of soft tissue sarcomas in the Netherlands:A population-based study

Introduction: Timely recognition of soft tissue sarcomas (STS) remains challenging, potentially leading to unplanned excisions (also known as 'whoops procedures'). This population-based study charted the occurrence of unplanned excisions and identified associated patient, tumour, and treatment-related characteristics. Furthermore, it presents an overview of the outcomes and clinical management following an unplanned excision. Methods: From the Netherlands Cancer Registry (NCR) database, information was obtained on 2187 adult patients diagnosed with STS in 2016-2019 who underwent surgery. Tumours located in the mediastinum, heart or retroperitoneum were excluded, as well as incidental findings. Differences between patients with planned and unplanned excisions were assessed with chi-square tests and a multivariable logistic regression model. Results: Overall, unplanned excisions comprise 18.2% of all first operations for STS, with a quarter of them occurring outside a hospital. Within hospitals, the unplanned excision rate was 14.4%. Unplanned excisions were more often performed on younger patients, and tumours unsuspected of being STS prior to surgery were generally smaller ( Discussion: Potential improvement in preventing unplanned excisions may be achieved by better compliance to preoperative imaging and referral guidelines, and stimulating continuous awareness of STS among general surgeons, general practitioners and private practices. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved