Modeling of the HIV infection epidemic in the Netherlands: A multi-parameter evidence synthesis approach

Multi-parameter evidence synthesis (MPES) is receiving growing attention from the epidemiological community as a coherent and flexible analytical framework to accommodate a disparate body of evidence available to inform disease incidence and prevalence estimation. MPES is the statistical methodology adopted by the Health Protection Agency in the UK for its annual national assessment of the HIV epidemic, and is acknowledged by the World Health Organization and UNAIDS as a valuable technique for the estimation of adult HIV prevalence from surveillance data. This paper describes the results of utilizing a Bayesian MPES approach to model HIV prevalence in the Netherlands at the end of 2007, using an array of field data from different study designs on various population risk subgroups and with a varying degree of regional coverage. Auxiliary data and expert opinion were additionally incorporated to resolve issues arising from biased, insufficient or inconsistent evidence. This case study offers a demonstration of the ability of MPES to naturally integrate and critically reconcile disparate and heterogeneous sources of evidence, while producing reliable estimates of HIV prevalence used to support public health decision-making.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS488 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The use and impact of European Testing Week regional awareness campaigns to increase HIV and viral hepatitis testing coverage

Introduction Since 2013, the European Testing Week (ETW) awareness campaign has become a key regional event influencing testing efforts for HIV, viral hepatitis, and sexually transmitted infections (STIs) through participation of 720 organizations. Here, we report on a survey from May to June 2022 aimed at assessing the participant-reported impact of the campaign. Methods All past and current participating organizations were asked to complete an online questionnaire between 12 May and 17 June 2022. Multiple choice and open-text questions included organization information, usage of ETW to engage in local testing-related activities, and the effect of a regional campaign to reach a wider audience and generate impact. Results Of the 52 respondents, 34 (65%) stated first participating in ETW 5–10 years ago. ETW was used for awareness raising by 40 respondents (83%), new testing activities by 37 (77%), advocacy initiatives by 15 (31%), and training/capacity building by 18 (38%). For awareness raising, 95% used ETW to highlight the importance of and to encourage testing; for new testing activities, 74% used ETW to reach new groups. In total, 44 (85%) reported added benefits of a Europe-wide campaign compared with national/local campaigns, particularly the increased visibility and collaboration opportunities. Impact at the local level was observed by 24 (51%), and impact at a national level was observed by 20 (43%). A total of 28 (79%) reported increases in the number of tests performed and 25 (75%) reported increases in clients accessing services. Conclusions Regional awareness campaigns reach wider audiences, boost local and national efforts to increase testing, and sensitize key populations about the critical value of testing compared with local/national campaigns.info:eu-repo/semantics/publishedVersio

The HepHIV 2023 Madrid conference: A call to action for political leadership in reaching the sustainable development goals on earlier testing and linkage to care for HIV, viral hepatitis, and sexually transmitted infections

Introduction and Objectives: The HepHIV 2023 Conference, held in Madrid in November 2023, highlighted how Europe is not on track to meet the United Nations (UN) sustainable development goals and Joint UN Programme on HIV/AIDS (UNAIDS) targets. This article presents the outcomes of the conference, which focus on ways to improve testing and linkage to care for HIV, viral hepatitis, and other sexually transmitted infections. HIV-related stigma and discrimination, a major barrier to progress, was a key concept of the conference and on the agenda of the Spanish Presidency of the European Union. Methods: The HepHIV 2023 organizing committee, alongside the Spanish Ministry of Health, oversaw the conference organization and prepared the scientific programme based on abstract rankings. Key outcomes are derived from conference presentations and discussions. Results: Conference presentations covered the obstacles that HIV-related stigma and discrimination continue to pose to access to services, models for data collection to better monitor progress in the future, and examples of legislative action that can be taken at national levels. Diversification of testing approaches was also highlighted, to reach key populations, (e.g. migrant populations), to increase testing offered in healthcare settings (e.g. emergency departments), and to account for different stages of epidemics across the region. Conclusion: With a strong call for intensified action to address the impact of HIV-related stigma and discrimination on testing uptake, the conference concluded that strengthened collaboration is required between governments and implementers around testing and linkage to care. There is also an ongoing need to ensure sustainable political commitment and appropriate resource allocation to address gaps and inequalities in access for key populations and to focus on the implementation of integrated responses to HIV, viral hepatitis, and sexually transmitted infections. © 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association

Functional Analysis of Ficolin-3 Mediated Complement Activation

The recognition molecules of the lectin complement pathway are mannose-binding lectin and Ficolin -1, -2 and -3. Recently deficiency of Ficolin-3 was found to be associated with life threatening infections. Thus, we aimed to develop a functional method based on the ELISA platform for evaluating Ficolin-3 mediated complement activation that could be applicable for research and clinical use. Bovine serum albumin (BSA) was acetylated (acBSA) and chosen as a solid phase ligand for Ficolins in microtiter wells. Binding of Ficolins on acBSA was evaluated, as was functional complement activation assessed by C4, C3 and terminal complement complex (TCC) deposition. Serum Ficolin-3 bound to acBSA in a calcium dependent manner, while only minimal binding of Ficolin-2 and no binding of Ficolin-1 were observed. No binding to normal BSA was seen for any of the Ficolins. Serum C4, C3 and TCC deposition on acBSA were dependent only on Ficolin-3 in appropriate serum dilutions. Deposition of down stream complement components correlated highly significantly with the serum concentration of Ficolin-3 but not with Ficolin-2 in healthy donors. To make the assay robust for clinical use a chemical compound was applied to the samples that inhibited interference from the classical pathway due to the presence of anti-BSA antibodies in some sera. We describe a novel functional method for measuring complement activation mediated by Ficolin-3 in human serum up to the formation of TCC. The assay provides the possibility to diagnose functional and genetic defects of Ficolin-3 and down stream components in the lectin complement pathway

The scope of language contact as a constraint factor in language change: The periphrasis haber de plus infinitive in a corpus of language immediacy in modern Spanish

In this work an empirical study grounded in the principles and methods of the comparative variationist framework is conducted to measure the scope of language contact as a factor constraining some potentially diverging uses of a Spanish verbal periphrasis that has undergone a sharp decline over the last century (haber de plus infinitive). The analysis is based on three independent samples of text that correspond to three dialectal areas of peninsular Spanish (monolingual zones, Catalan-speaking linguistic territories and the north-western linguistic area). These samples, extracted from a corpus made up of texts of communicative immediacy from the 19th and the first half of the 20th centuries, confirm the existence of a certain linguistic convergence in the expressive habits of the speakers in the bilingual communities. In each region, however, the outcomes are different, due to parallel differences in the structural position of the periphrasis in each language. However, a thorough analysis of the variable context that surrounds the periphrasis shows that the observed differences do not affect the essence of the underlying grammar of this variant, whose decline (which favours tener que plus infinitive and becomes faster as the 20th century advances) is constrained by identical linguistic and extralinguistic conditioning factors in all the dialectal areas

Local Inflammation Induces Complement Crosstalk Which Amplifies the Antimicrobial Response

By eliciting inflammatory responses, the human immunosurveillance system notably combats invading pathogens, during which acute phase proteins (CRP and cytokines) are elevated markedly. However, the Pseudomonas aeruginosa is a persistent opportunistic pathogen prevalent at the site of local inflammation, and its acquisition of multiple antibiotic-resistance factors poses grave challenges to patient healthcare management. Using blood samples from infected patients, we demonstrate that P. aeruginosa is effectively killed in the plasma under defined local infection-inflammation condition, where slight acidosis and reduced calcium levels (pH 6.5, 2 mM calcium) typically prevail. We showed that this powerful antimicrobial activity is provoked by crosstalk between two plasma proteins; CRP∶L-ficolin interaction led to communication between the complement classical and lectin pathways from which two amplification events emerged. Assays for C4 deposition, phagocytosis, and protein competition consistently proved the functional significance of the amplification pathways in boosting complement-mediated antimicrobial activity. The infection-inflammation condition induced a 100-fold increase in CRP∶L-ficolin interaction in a pH- and calcium-sensitive manner. We conclude that the infection-induced local inflammatory conditions trigger a strong interaction between CRP∶L-ficolin, eliciting complement-amplification pathways which are autonomous and which co-exist with and reinforce the classical and lectin pathways. Our findings provide new insights into the host immune response to P. aeruginosa infection under pathological conditions and the potential development of new therapeutic strategies against bacterial infection

Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours

The SPECTRA Collaboration OMERACT Special Interest Group: Current Research and Future Directions

Objective High-resolution peripheral quantitative computed tomography (HR-pQCT) has the potential to improve radiographic progression determination in clinical trials and longitudinal observational studies. The goal of this work was to describe the current state of research presented at Outcome Measures in Rheumatology (OMERACT) 2016 and ensuing future directions outlined during discussion among attendees. Methods At OMERACT 2016, SPECTRA (Study grouP for xtrEme-Computed Tomography in Rheumatoid Arthritis) introduced efforts to (1) validate the HR-pQCT according to OMERACT guidelines, focusing on rheumatoid arthritis (RA), and (2) find alternatives for automated joint space width (JSW) analysis. The Special Interest Group (SIG) was presented to patient research partners, physicians/researchers, and SIG leaders followed by a 40-min discussion on future directions. Results A consensus definition for RA erosion using HR-pQCT was demonstrated through a systematic literature review and a Delphi exercise. Histopathology and perfusion studies were presented that analyzed the true characteristics of cortical breaks in HR-pQCT images, and to provide criterion validity. Results indicate that readers were able to discriminate between erosion and small vascular channels. Moderate reliability (ICC 0.206–0.871) of direct erosion size measures was shown, which improved (> 0.9) only when experienced readers were considered. Quantification of erosion size was presented for scoring, direct measurement, and volumetric approaches, as well as a reliability exercise for direct measurement. Three methods for JSW measurement were compared, all indicating excellent reproducibility with differences at the extremes (i.e., near-zero and joint edge thickness). Conclusion Initial reports on HR-pQCT are promising; however, to consider its use in clinical trials and longitudinal observational studies, it is imperative to assess the responsiveness of erosion measurement quantification