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3. Measuring the uptake of clinic-based HIV treatment and prevention services following HIV testing and referral at private pharmacies in Kenya

Author

Victor Omollo, Stephanie D. Roche, Shengruo Zhang, Magdalene Asewe, Bernard K. Rono, Benn Kwach, Greshon Rota, Patricia Ong’wen, Kendall Harkey, Josephine Odoyo, Daniel Were, Kenneth Ngure, Elizabeth A. Bukusi, and Katrina F. Ortblad

Subjects
HIV testing, PrEP, PEP, ART, Linkage to care, Private pharmacies, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Despite their ubiquity across sub-Saharan Africa, private pharmacies are underutilized for HIV service delivery beyond the sale of HIV self-test kits. To understand what uptake of HIV prevention and treatment services might look like if private pharmacies offered clients free HIV self-testing and referral to clinic-based HIV services, we conducted a pilot study in Kenya. Methods At 20 private pharmacies in Kisumu County, Kenya, pharmacy clients (≥ 18 years) purchasing sexual health-related products (e.g., contraception) were offered free HIV testing. Based on their test result and recent self-reported behaviors associated with HIV risk, clients were encouraged to consider pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), or antiretroviral therapy (ART) initiation, informed where they could access free services, and issued a referral. We called clients three months after study completion to see if they had initiated the recommended service. Among clients who reported PrEP referral, we used Poisson regression models to examine characteristics associated with PrEP initiation and calculated adjusted prevalence ratios (aPRs). Results From March to June 2022, 1500 pharmacy clients completed HIV testing and were referred to clinic-based HIV services; in October 2022, 1178 (79%) were reached and meet our criteria for follow-up. Among those reached, the majority (63%, 742/1178) were women, the median age was 26 years (IQR 22–31), and few (4%, 51/1178) reported any prior PrEP use. At the pharmacy, most clients (96%, 1136/1178) tested HIV-negative and reported PrEP (95%, 1122/1178) or PEP (1%, 14/1178) referral; the remainder (4%, 42/1178) tested HIV-positive and reported ART referral. The uptake of ART (90%, 38/42) and PEP (86%, 12/14) among clients referred was high. The uptake of PrEP was only 9% (101/1122) among those referred and prior PrEP use was the only characteristic significantly associated with initiation (aPR 2.45, 95% confidence interval 1.19 to 5.07). Conclusions Although offering free HIV testing at private pharmacies led to the identification and referral of clients who could benefit from HIV services, additional interventions (e.g., incentives, patient navigators) may be needed to support PrEP referral follow-through. Alternatively, new delivery models that circumvent the need for referrals, such as same-day PrEP initiation at pharmacies, should be considered.

Published
2025
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4. miR-449a/miR-340 reprogram cell identity and metabolism in fusion-negative rhabdomyosarcoma

Author

Enrico Pozzo, Laura Yedigaryan, Nefele Giarratana, Chao-chi Wang, Gabriel Miró Garrido, Ewoud Degreef, Vittoria Marini, Gianmarco Rinaldi, Bernard K. van der Veer, Gabriele Sassi, Guy Eelen, Mélanie Planque, Alessandro Fanzani, Kian Peng Koh, Peter Carmeliet, Jason T. Yustein, Sarah-Maria Fendt, Anne Uyttebroeck, and Maurilio Sampaolesi

Subjects
CP: Cancer, Biology (General), QH301-705.5
Abstract

Summary: Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, arises in skeletal muscle and remains in an undifferentiated state due to transcriptional and post-transcriptional regulators. Among its subtypes, fusion-negative RMS (FN-RMS) accounts for the majority of diagnoses in the pediatric population. MicroRNAs (miRNAs) are non-coding RNAs that modulate cell identity via post-transcriptional regulation of messenger RNAs (mRNAs). In this study, we identify miRNAs impacting FN-RMS cell identity, revealing miR-449a and miR-340 as major regulators of the cell cycle and p53 signaling. Through miR-eCLIP technology, we demonstrate that miR-449a and miR-340 directly target transcripts involved in glycolysis and mitochondrial pyruvate transport, inhibiting the mitochondrial pyruvate carrier (MPC) complex. Pharmacological MPC inhibition induces a similar metabolic shift, reducing metastatic potential and leading to cell cycle exit. Overall, miR-449 and miR-340 orchestrate FN-RMS cell identity, positioning MPC inhibition as a strategy to shift FN-RMS cells toward a non-tumorigenic, quiescent state.

Published
2025
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6. Antimicrobial activity, toxicity and retrospective clinical effectiveness of Kantinka BA and Kantinka Herbaltics, two multi-component-herbal products used in the management of infectious diseases in Ghana

Author

Bernard K. Turkson, Desmond Nkrumah, Reinhard Isaac Nketia, Alfred Ofori Agyemang, Isaac Kingsley Amponsah, Burnett Tetteh Accam, Merlin L.K. Mensah, and Yvonne Boateng

Subjects
Antimicrobial agents, phytochemical screening, gastritis, Candida albicans, Neisseria gonorrhoeae, Acquired Immunodeficiency Syndrome, Botany, QK1-989, Medicine
Abstract

There is an upsurge in the incidence of persons living with infectious diseases and their associated symptoms. Also, there is increased resistance and high cost of available synthetic antimicrobial therapeutic agents. This calls for screening candidate herbal products to examine the risk-to-benefit ratio for users. Moreover, there are inadequate proven scientific studies to assess the quality, effectiveness, and toxicity of herbal products that traditional medicine practitioners in Ghana commonly use for the management of infectious diseases such as those caused by Neisseria gonorrhoeae, Candida albicans and the symptomatic management of symptoms associated with infections like cough, skin infections among others and gastritis. Kantinka BA and Kantinka Herbaltics, two multicomponent herbal products, have been used to manage the above-mentioned disease conditions. The study aims to evaluate the in vitro antibacterial activity, assess the retrospective clinical effectiveness (clinical responses; the disappearance of presenting signs and symptoms associated with infections, gastritis), and the quality and toxicity of Kantinka BA and Kantinka Herbaltics. The products are registered by the Food and Drugs Authority (FDA). Data on 200 patients who were diagnosed with infectious diseases such as Human Immunodeficiency Virus (HIV) / Acquired Immunodeficiency Syndrome (AIDS) and associated symptoms from January 2018 to June 2018 was obtained from the Adom Herbal Clinic, and the Tafo Government Herbal Medicine Records Unit was assessed. The antibacterial activity of the products was evaluated using the HT-SPOTi method. Phytochemical screening, microbial load, and pH were carried out according to standard procedures. Acute toxicity was carried out according to the Organization for Economic Cooperation and Development (OECD) guideline 425. Phytochemical screening, pH, and microbial load have been established for both products. Binding toxicity studies revealed that the products are non-toxic at a 2000 mg/kg dose. The two products exhibited antimicrobial activities against the test organisms with Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) determined for Kantinka BA and Kantinka Herbaltics as 5% and 10% and

Published
2024
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8. The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency

Author

Athanasouli, Paraskevi, Balli, Martina, De Jaime-Soguero, Anchel, Boel, Annekatrien, Papanikolaou, Sofia, van der Veer, Bernard K., Janiszewski, Adrian, Vanhessche, Tijs, Francis, Annick, El Laithy, Youssef, Nigro, Antonio Lo, Aulicino, Francesco, Koh, Kian Peng, Pasque, Vincent, Cosma, Maria Pia, Verfaillie, Catherine, Zwijsen, An, Heindryckx, Björn, Nikolaou, Christoforos, and Lluis, Frederic

Published
2023
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11. Spatially Self‐Organized Three‐Dimensional Neural Concentroid as a Novel Reductionist Humanized Model to Study Neurovascular Development

Author

Yoke Chin Chai, San Kit To, Susan Simorgh, Samantha Zaunz, YingLi Zhu, Karan Ahuja, Alix Lemaitre, Roya Ramezankhani, Bernard K. van derVeer, Keimpe Wierda, Stefaan Verhulst, Leo A. vanGrunsven, Vincent Pasque, and Catherine Verfaillie

Subjects
blood‐brain barrier, brain organoids, neurovascular, vascularization, Science
Abstract

Abstract Although human pluripotent stem cell (PSC)‐derived brain organoids have enabled researchers to gain insight into human brain development and disease, these organoids contain solely ectodermal cells and are not vascularized as occurs during brain development. Here it is created less complex and more homogenous large neural constructs starting from PSC‐derived neuroprogenitor cells (NPC), by fusing small NPC spheroids into so‐called concentroids. Such concentroids consisted of a pro‐angiogenic core, containing neuronal and outer radial glia cells, surrounded by an astroglia‐dense outer layer. Incorporating PSC‐derived endothelial cells (EC) around and/or in the concentroids promoted vascularization, accompanied by differential outgrowth and differentiation of neuronal and astroglia cells, as well as the development of ectodermal‐derived pericyte‐like mural cells co‐localizing with EC networks. Single nucleus transcriptomic analysis revealed an enhanced neural cell subtype maturation and diversity in EC‐containing concentroids, which better resemble the fetal human brain compared to classical organoids or NPC‐only concentroids. This PSC‐derived “vascularized” concentroid brain model will facilitate the study of neurovascular/blood‐brain barrier development, neural cell migration, and the development of effective in vitro vascularization strategies of brain mimics.

Published
2024
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12. Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling

Author

Jonathan Sai‐Hong Chui, Teresa Izuel‐Idoype, Alessandra Qualizza, Rita Pires deAlmeida, Lindsey Piessens, Bernard K. van derVeer, Gert Vanmarcke, Aneta Malesa, Paraskevi Athanasouli, Ruben Boon, Joris Vriens, Leo vanGrunsven, Kian Peng Koh, Catherine M. Verfaillie, and Frederic Lluis

Subjects
hepatic model, stem cell differentiation, cell cycle, WNT signaling, NF‐kB signaling, Science
Abstract

Abstract Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to differentiate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces a protective p53‐independent quiescent state in immature hepatoma cells and in pluripotent stem cell‐derived models of human hepatocytes and endothelial cells. Prolonged culture in hyperosmolar conditions stimulates changes in gene expression promoting functional cell maturation. Interestingly, hyperosmolar conditions do not only trigger growth arrest and cellular maturation but are also necessary to maintain this maturated state, as switching back to plasma osmolarity reverses the changes in expression of maturation and proliferative markers. Transcriptome analysis revealed sequential stages of osmolarity‐regulated growth arrest followed by cell maturation, mediated by activation of NF‐κВ, and repression of WNT signaling, respectively. This study reveals that a modulated increase in osmolarity serves as a biochemical signal to promote long‐term growth arrest and cellular maturation into different lineages, providing a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely.

Published
2024
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15. A scoping review of zoonotic parasites and pathogens associated with abattoirs in Eastern Africa and recommendations for abattoirs as disease surveillance sites

Author

Katie A. Rodarte, Jeanne M. Fair, Bernard K. Bett, Susan D. Kerfua, Folorunso O. Fasina, and Andrew W. Bartlow

Subjects
abattoir, slaughterhouses, livestock, zoonotic disease, one health, Public aspects of medicine, RA1-1270
Abstract

Abattoirs are facilities where livestock are slaughtered and are an important aspect in the food production chain. There are several types of abattoirs, which differ in infrastructure and facilities, sanitation and PPE practices, and adherence to regulations. In each abattoir facility, worker exposure to animals and animal products increases their risk of infection from zoonotic pathogens. Backyard abattoirs and slaughter slabs have the highest risk of pathogen transmission because of substandard hygiene practices and minimal infrastructure. These abattoir conditions can often contribute to environmental contamination and may play a significant role in disease outbreaks within communities. To assess further the risk of disease, we conducted a scoping review of parasites and pathogens among livestock and human workers in abattoirs across 13 Eastern African countries, which are hotspots for zoonoses. Our search results (n = 104 articles) showed the presence of bacteria, viruses, fungi, and macroparasites (nematodes, cestodes, etc.) in cattle, goats, sheep, pigs, camels, and poultry. Most articles reported results from cattle, and the most frequent pathogen detected was Mycobacterium bovis, which causes bovine tuberculosis. Some articles included worker survey and questionnaires that suggested how the use of PPE along with proper worker training and safe animal handling practices could reduce disease risk. Based on these findings, we discuss ways to improve abattoir biosafety and increase biosurveillance for disease control and mitigation. Abattoirs are a ‘catch all’ for pathogens, and by surveying animals at abattoirs, health officials can determine which diseases are prevalent in different regions and which pathogens are most likely transmitted from wildlife to livestock. We suggest a regional approach to biosurveillance, which will improve testing and data gathering for enhanced disease risk mapping and forecasting. Next generation sequencing will be key in identifying a wide range of pathogens, rather than a targeted approach.

Published
2023
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16. Measuring the uptake of clinic-based HIV treatment and prevention services following HIV testing and referral at private pharmacies in Kenya.

Author

Omollo, Victor, Roche, Stephanie D., Zhang, Shengruo, Asewe, Magdalene, Rono, Bernard K., Kwach, Benn, Rota, Greshon, Ong'wen, Patricia, Harkey, Kendall, Odoyo, Josephine, Were, Daniel, Ngure, Kenneth, Bukusi, Elizabeth A., and Ortblad, Katrina F.

Subjects
HIV testing kits, DIAGNOSIS of HIV infections, PATIENT self-monitoring, HIV prevention, POISSON regression, PRE-exposure prophylaxis
Abstract

Background: Despite their ubiquity across sub-Saharan Africa, private pharmacies are underutilized for HIV service delivery beyond the sale of HIV self-test kits. To understand what uptake of HIV prevention and treatment services might look like if private pharmacies offered clients free HIV self-testing and referral to clinic-based HIV services, we conducted a pilot study in Kenya. Methods: At 20 private pharmacies in Kisumu County, Kenya, pharmacy clients (≥ 18 years) purchasing sexual health-related products (e.g., contraception) were offered free HIV testing. Based on their test result and recent self-reported behaviors associated with HIV risk, clients were encouraged to consider pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), or antiretroviral therapy (ART) initiation, informed where they could access free services, and issued a referral. We called clients three months after study completion to see if they had initiated the recommended service. Among clients who reported PrEP referral, we used Poisson regression models to examine characteristics associated with PrEP initiation and calculated adjusted prevalence ratios (aPRs). Results: From March to June 2022, 1500 pharmacy clients completed HIV testing and were referred to clinic-based HIV services; in October 2022, 1178 (79%) were reached and meet our criteria for follow-up. Among those reached, the majority (63%, 742/1178) were women, the median age was 26 years (IQR 22–31), and few (4%, 51/1178) reported any prior PrEP use. At the pharmacy, most clients (96%, 1136/1178) tested HIV-negative and reported PrEP (95%, 1122/1178) or PEP (1%, 14/1178) referral; the remainder (4%, 42/1178) tested HIV-positive and reported ART referral. The uptake of ART (90%, 38/42) and PEP (86%, 12/14) among clients referred was high. The uptake of PrEP was only 9% (101/1122) among those referred and prior PrEP use was the only characteristic significantly associated with initiation (aPR 2.45, 95% confidence interval 1.19 to 5.07). Conclusions: Although offering free HIV testing at private pharmacies led to the identification and referral of clients who could benefit from HIV services, additional interventions (e.g., incentives, patient navigators) may be needed to support PrEP referral follow-through. Alternatively, new delivery models that circumvent the need for referrals, such as same-day PrEP initiation at pharmacies, should be considered. [ABSTRACT FROM AUTHOR]

Published
2025
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17. Micro‐Topographies Induce Epigenetic Reprogramming and Quiescence in Human Mesenchymal Stem Cells

Author

Steven Vermeulen, Bart Van Puyvelde, Laura Bengtsson del Barrio, Ruben Almey, Bernard K. van derVeer, Dieter Deforce, Maarten Dhaenens, and Jan de Boer

Subjects
biomaterials, epigenetics, mechanobiology, mesenchymal stem cells, nucleus, Science
Abstract

Abstract Biomaterials can control cell and nuclear morphology. Since the shape of the nucleus influences chromatin architecture, gene expression and cell identity, surface topography can control cell phenotype. This study provides fundamental insights into how surface topography influences nuclear morphology, histone modifications, and expression of histone‐associated proteins through advanced histone mass spectrometry and microarray analysis. The authors find that nuclear confinement is associated with a loss of histone acetylation and nucleoli abundance, while pathway analysis reveals a substantial reduction in gene expression associated with chromosome organization. In light of previous observations where the authors found a decrease in proliferation and metabolism induced by micro‐topographies, they connect these findings with a quiescent phenotype in mesenchymal stem cells, as further shown by a reduction of ribosomal proteins and the maintenance of multipotency on micro‐topographies after long‐term culture conditions. Also, this influence of micro‐topographies on nuclear morphology and proliferation is reversible, as shown by a return of proliferation when re‐cultured on a flat surface. The findings provide novel insights into how biophysical signaling influences the epigenetic landscape and subsequent cellular phenotype.

Published
2023
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18. Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions

Author

Laura Yedigaryan, Ester Martínez-Sarrà, Giorgia Giacomazzi, Nefele Giarratana, Bernard K. van der Veer, Alessio Rotini, Silvia Querceto, Hanne Grosemans, Álvaro Cortés-Calabuig, Sara Salucci, Michela Battistelli, Elisabetta Falcieri, Rik Gijsbers, Mattia Quattrocelli, Kian Peng Koh, Liesbeth De Waele, Gunnar M. Buyse, Rita Derua, and Maurilio Sampaolesi

Subjects
extracellular vesicle, hypertrophy, muscular dystrophy, aging, miRNA, skeletal muscle, Immunologic diseases. Allergy, RC581-607
Abstract

Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo, and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength, cross-sectional area, and fibrosis compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells.

Published
2022
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24. From policy to practice: An assessment of biosecurity practices in cattle, sheep and goats production, marketing and slaughter in Baringo County, Kenya.

Author

Edna N Mutua, Bernard K Bett, Salome A Bukachi, Benson A Estambale, and Isaac K Nyamongo

Subjects
Medicine, Science
Abstract

Globally, biosecurity is instrumental in prevention, control and management of livestock diseases and protection of human health. It is defined, prescribed, adopted and enforced through global, regional and national frameworks, laws, policies and strategies. There is more biosecurity practice research conducted in developed countries than developing ones. Consequently, the gap between the ideals recommended in biosecurity frameworks and what is practical in under-resourced rural settings is poorly understood. This anthropological study sought to assess adoption of biosecurity practices across a cattle, sheep and goat value chains continuum to demonstrate where risks lie. The cross-sectional mixed-methods study took place in Baringo County, Kenya. Qualitatively, it utilized 26 focus group discussions with community members and 10 observational interviews with slaughter facility workers. Quantitatively, it included a household survey with 560 community members and a separate survey with 231 livestock traders. Results show that producers, traders and slaughter facility workers did observe some biosecurity practices but not others due but not limited to personal preference, limitations in veterinary service delivery and enforcement of some biosecurity measures, and lack of requisite infrastructure. The study concludes that the implementation of biosecurity measures in rural settings is more complex than envisioned in biosecurity policies and frameworks. It can be hampered by resource limitations, poor enforcement, and contestations with cultural practices. The study recommends that further studies on willingness to adopt biosecurity measures targeting community members in under-resourced settings be conducted to identify possible critical points of intervention at county and national levels.

Published
2022
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25. The Monongahela tradition in 'real time': Bayesian analysis of radiocarbon dates.

Author

John P Hart and Bernard K Means

Subjects
Medicine, Science
Abstract

Despite advances in techniques, methods, and theory, northeastern North American archaeologists continue to use early to mid-twentieth century culture historical taxa as units of analysis and narrative. There is a distinct need to move away from this archaeological practice to enable fuller understandings of past human lives. One tool that enables such a move is Bayesian analysis of radiocarbon dates, which provides a means of constructing continuous chronologies. A large dataset of radiocarbon dates for late prehistoric (ca AD 900/1000-1650) sites in the lower upper Ohio River basin in southwestern Pennsylvania and adjacent portions of Maryland, Ohio, and West Virginia is used here as an example. The results allow a preliminary assessment of how the settlement plans of contemporaneous villages varied considerably, reflecting decisions of the village occupants how to structure built environments to meet their needs.

Published
2022
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26. PT-symmetric quantum state discrimination

Author

Bender, Carl M., Brody, Dorje C., Caldeira, Joao, and Meister, Bernard K.

Subjects
High Energy Physics - Theory, Mathematical Physics, Quantum Physics
Abstract

Suppose that a system is known to be in one of two quantum states, $|\psi_1 > $ or $|\psi_2 >$. If these states are not orthogonal, then in conventional quantum mechanics it is impossible with one measurement to determine with certainty which state the system is in. However, because a non-Hermitian PT-symmetric Hamiltonian determines the inner product that is appropriate for the Hilbert space of physical states, it is always possible to choose this inner product so that the two states $|\psi_1 > $ and $|\psi_2 > $ are orthogonal. Thus, quantum state discrimination can, in principle, be achieved with a single measurement., Comment: 4 pages, no figures

Published
2010
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28. Wnt/β-Catenin Inhibition Disrupts Carboplatin Resistance in Isogenic Models of Triple-Negative Breast Cancer

Author

Willy Antoni Abreu de Oliveira, Stijn Moens, Youssef El Laithy, Bernard K. van der Veer, Paraskevi Athanasouli, Emanuela Elsa Cortesi, Maria Francesca Baietti, Kian Peng Koh, Juan-Jose Ventura, Frédéric Amant, Daniela Annibali, and Frederic Lluis

Subjects
triple negative breast cancer, WNT pathway, platinum-resistance, cancer stem cells, patient-derived xenograft models, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metastatic settings. However, primary and acquired resistance to chemotherapy in general and platinum-based regimens specifically strongly hampers TNBC management. In this study, we used carboplatin-resistant in vivo patient-derived xenograft and isogenic TNBC cell-line models and detected enhanced Wnt/β-catenin activity correlating with an induced expression of stem cell markers in both resistant models. In accordance, the activation of canonical Wnt signaling in parental TNBC cell lines increases stem cell markers’ expression, formation of tumorspheres and promotes carboplatin resistance. Finally, we prove that Wnt signaling inhibition resensitizes resistant models to carboplatin both in vitro and in vivo, suggesting the synergistic use of Wnt inhibitors and carboplatin as a therapeutic option in TNBC. Here we provide evidence for a prominent role of Wnt signaling in mediating resistance to carboplatin, and we establish that combinatorial targeting of Wnt signaling overcomes carboplatin resistance enhancing chemotherapeutic drug efficacy.

Published
2021
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31. Identification and Characteristics of Source Rocks in Lt-1 Well, Northern Kenya

Author

Bernard K. Rop, Faith F. Mlewa, Fatuma Rajab Mwanganga, Deng Andrew Mayik, and Gatluok Koang Gach

Subjects
Computer Networks and Communications, Hardware and Architecture, Software
Abstract

This study on the hydrocarbon source rocks identification of LT-1 well in a Tertiary rift basin, northern Kenya, which had oil and gas shows was based on the organic matter quantity, quality, and the thermal maturation generation capability of the organic matter disseminated in the analysed rock samples. The organic matter contents were determined directly from laboratory analyses of the source rock samples with the help of seismic and gamma-ray profiles, total organic carbon (TOC wt%), maturity indices (HI and PI), temperature maximum (Tmax °C), porosities and other sedimentological parameters. This study involved a series of analytical geochemistry and petro-physical studies in ascertaining a number of effective source rock samples from the well cores which were then analysed in terms of TOC, PI, HI, S2, S1 and Tmax to determine oil/gas prone samples (resource areas) and distinguish them from strata with very high organic matter content. The samples with very high TOC were identified for possible source rock characterisations of the lithology pertaining to the well in terms of potential source-reservoir-seals associations. The Rock-Eval pyrolysis data were useful in assessing and evaluating the type of organic matter, thermal maturity, and the generation capability of source rocks for hydrocarbon exploration rationale. The analyses revealed that some strata within the sampled well data have high hydrocarbon generation potential with the existence of commercial hydrocarbon production. In conclusion, after an in-depth comparison and study of organic carbon content, hydrogen and production indices, type of organic matter content and maturity of organic matter, we confirmed that the studied resource areas are favourably considered for medium- to large-size hydrocarbon discoveries.

Published
2023
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32. Influence of species diversity on the return of ecosystem functions in replanted mangroves in Kenya

Author

Kirui, Bernard K. Y. and Huxham, Mark

Subjects
634.9, QK Botany
Abstract

Rates of loss of biodiversity caused by human action are on the increase worldwide. However implications of species loss on the natures' ability to provide ecosystem services and goods are still poorly understood. Despite providing an array of critical services and goods, mangrove ecosystems are under intense threat. In attempts to address the problem, several mangrove restoration initiatives have been formulated in many areas of the world with different objectives. Over the last two decades, experiments manipulating species diversity and measuring ecosystem functions have been conducted mainly using grassland ecosystems and have exhibited positive relationships. More recently, experiments investigating this relationship have emerged in longterm woody species i.e. trees; however these have concentrated on terrestrial forests. This study experimentally manipulated different mangrove species and measured a range of ecosystem functions including sapling survival, above and below ground biomass production and sediment C02 efflux. Enhanced sapling growth was positively correlated with plot height above datum, percentage silt and nitrates and negatively correlated with sediment salinity, ammonium and phosphates. Also high values of above and below ground biomass, root: shoot ratios, mean tree height, leaf area index as well as naturally recruited saplings were observed in mixed plots (particularly with Avicennia marina in the mixture) compared with monospecific plots. Species selection effect, particularly from the fast growing A. marina species was the mechanism behind a range of the observed ecosystem functions. However complementarily effects were observed particularly on above ground biomass. However sapling survival and sediment CO2 efflux was not influenced by species richness. We conclude that there is variation in the stages of plant development at which species richness effects manifest themselves, in addition the effects of environmental variables has a bearing on the nature and direction of the relationship between species richness and ecosystem function. We anticipate changes in the plots structure over time from A vicennia facilitative effects which are expected to lead to changes in sediment microclimate inducing changes in other species growth and promoting recruitment and development of wildlings.

Published
2008

35. Predictors of Girls’ Performance in Mathematics among Senior High School Students

Author

Abdulai B.I., Christopher S.B., Francis X.A., Bernard K., Stephen A., Lloyd O., Grace M.B., and Dennis O.K.

Abstract

The study employed the Explanatory Sequential design of the Mixed-Methods approach to investigate the factors that affect female students’ performance in mathematics. Stratified and Simple Random Sampling techniques were used to sample three hundred and fifty-six (356) participants from four different Senior High Schools within the Northern Region to participate in the survey while 12 key informants were selected using the Expert Purposive Sampling technique for key informant interviews. Questionnaires and interview guides were the main instruments used for data collection. Inferential statistics were used to analyse the quantitative data while inductive thematic analysis was used in analysing the qualitative data. The results of the analyses showed that gender stereotypes, the socio-economic status of parents, self-motivation by the female students, the social environment in which the female students find themselves and teacher efficacy were the main factors affecting female students’ performance in mathematics.

Published
2023
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37. Awareness and Perceptions of Climate Variability Adaptation among Forest-adjacent Communities in Mau Forest, Kenya

Author

Grace W. Kibue, Bernard K. Kirui, and Stephen Mwangi

Abstract

Adequate knowledge of climate variability is essential for the success of any adaptation or mitigation efforts. Thus, a study was conducted to investigate the levels of awareness and perceptions on the adaptation of climate variability among forest-adjacent communities (FACs) in Mau Forest, Kenya. Data for the investigation was generated through the administration of 313 questionnaires across randomly selected forest-adjacent households. Of the entire questionnaire, 311 were analysed, while two were returned uncompleted and therefore discarded. Descriptive and inferential statistical analyses were conducted. Descriptive analysis showed that 96% of the respondents had knowledge of climate variability, while 4% claimed no knowledge of it. Nearly two-thirds of respondents (65%) reported that they receive weather information, with media (electronic and print) cited as the most common (63%) source of this information. As regards frequency of information, those respondents who get information about climate variability occasionally constituted 60%, while 29% of respondents received information frequently. However, 14% of respondents rarely received any climate-related information. Respondents who received climate-related information occasionally (sometimes) constituted 56%. Alternatively, respondents reported that they obtained weather information from agricultural extension officers (17.6%) and Kenya Forestry Service (KFS) officials (15.3%). The perceptions of the farmers that they had observed erratic weather patterns with a general decline in rainfall and an increase in temperatures were corroborated by scientific data as a trend analysis on rainfall and temperature data over a 20-year period mirrored the farmer’s perceptions. A logistic regression model was fitted to determine the socioeconomic factors that influence farmers’ choice of adaptation to climate variability. The ANOVA test results (F-test) show that overall, the logistic regression model was significant (df = 310, p = 0.002). Results of the model revealed that household head age (df = 310, p = 0.015), household head years of residency (df = 310, p = 0.034), and farming experience (df = 310, p = 0.024) were all significant factors that influence FACs’ decision to adopt to climate variability either positively or negatively. This study therefore recommends for more awareness creation and training of FACs of East Mau on how to identify and deal with changing climatic conditions.

Published
2022
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38. Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy

Author

Chammartin, F., Lodi, S., Logan, R., Ryom, L., Mocroft, A., Kirk, O., D'Arminio Monforte, A., Reiss, P., Phillips, A., El-Sadr, W., Hatleberg, C. I., Pradier, C., Bonnet, F., Law, M., De Wit, S., Sabin, C., Lundgren, J. D., Bucher, H. C., Calvo, G., Dabis, F., Morfeldt, L., Weber, R., Lind-Thomsen, A., Salbol Brandt, R., Hillebreght, M., Zaheri, S., Wit, F. W. N. M., Scherrer, A., Schoni-Affolter, F., Rickenbach, M., Tavelli, A., Fanti, I., Leleux, O., Mourali, J., Le Marec, F., Boerg, E., Thulin, E., Sundstrom, A., Bartsch, G., Thompsen, G., Necsoi, C., Delforge, M., Fontas, E., Caissotti, C., Dollet, K., Mateu, S., Torres, F., Petoumenos, K., Blance, A., Huang, R., Puhr, R., Gronborg Laut, K., Kristensen, D., Kamara, D. A., Smith, C. J., Raben, D., Matthews, C., Bojesen, A., Grevsen, A. L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Smit, C., Ross, M., Fux, C. A., Morlat, P., Friis-Moller, N., Kowalska, J., Bohlius, J., Bower, M., Fatkenheuer, G., Grulich, A., Sjol, A., Meidahl, P., Iversen, J. S., Hillebregt, M., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T. M., Godfried, M. H., Van Der Poll, T., Nellen, F. J. B., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., Van Der Valk, M., Goorhuis, A., Hovius, J. W., Van Eden, J., Henderiks, A., Van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., Van Den Berge, M., Stegeman, A., Baas, S., Hage De Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., Van Der Plas, A., Weijsenfeld, A. M., Van Der Ende, M. E., de Vries-Sluijs, T. E. M. S., van Gorp, E. C. M., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Van Der Feltz, M., Bassant, N., Van Beek, J. E. A., Vriesde, M., Van Zonneveld, L. M., De Oude-Lubbers, A., Van Den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., De Zeeuw-De Man, M., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Driessen, G. J. A., van Rossum, A. M. C., Van Der Knaap, L. C., Visser, E., Branger, J., Rijkeboer-Mes, A., Duijf-Van De Ven, C. J. H. M., Schippers, E. F., van Nieuwkoop, C., van IJperen, J. M., Geilings, J., van der Hut, G., Franck, P. F. H., Van Eeden, A., Brokking, W., Groot, M., Elsenburg, L. J. M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., Van Den Berg, J. F., Van Hulzen, A. G. W., Van Der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., Kroon, F. P., De Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Van Holten, N., Claas, E. C. J., Wessels, E., Den Hollander, J. G., Pogany, K., Roukens, A., Kastelijns, M., Smit, J. V., Smit, E., Struik-Kalkman, D., Tearno, C., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A. M. L., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg-Maes, B., van Loo, I. H. M., Havenith, T. R. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Smits, P. H. M., Weijer, S., El Moussaoui, R., Bosma, A. S., van Vonderen, M. G. A., van Houte, D. P. F., Kampschreur, L. M., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-Van de Plas, M., Heins, H., Lucas, E., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., van Truijen-Oud, F. A., van der Reijden, W. A., Jansen, R., Brinkman, K., van den Berk, G. E. L., Blok, W. L., Frissen, P. H. J., Lettinga, K. D., Schouten, W. E. M., Veenstra, J., Brouwer, J. C., Geerders, F. G., Hoeksema, K., Kleene, J. M., van der Meche, B. I., Spelbrink, M., Sulman, H., Toonen, A. J. M., Wijnands, S., Kwa, D., Witte, E., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, J. B., Stelma, F. F., Rahamat-Langendoen, J., Burger, D., Richter, C., Gisolf, H. E., Hassing, J. R., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., van der Swaluw, J., Bermon, N., Herpers, B. L., Veenendaal, D., Verhagen, W. D. M., van Wijk, M., van Kasteren, M. E. E., Brouwer, E. A., de Kruijf-Van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, H. J., Buiting, A. G. M., Kabel, J. P., Bierman, W. F. W., Scholvinck, H., Wilting, R. K., Stienstra, Y., de Groot-De Jonge, H., van der Meulen, A. P., de Weerd, A. D., Ludwig-Roukema, J., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Knoester, M., Hoepelman, A. I. M., Mudrikova, T., Ellerbroek, M. P., Oosterheert, J. J., Arends, E. J., Barth, E. R., Wassenberg, M. W. M., Schadd, M. E., van Elst-Laurijssen, D. H. M., van Oers-Hazelzet, B. E., Vervoort, S., van Berkel, M., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, A. M., Bomers, M., de Vocht, J., Heitmuller, M., Laan, M. L., Pettersson, M. A., Vandenbroucke-Grauls, C. M. J. E., Ang, W. C., Geelen, S. P. M., Wolfs, T. F. W., Bont, J. L., Nauta, N., Bezemer, O. D., van Sighem, I. A., Boender, S. T., de Jong, A., Bergsma, D., Hoekstra, P., de Lang, A., Grivell, S., Jansen, A., Rademaker, J. M., Raethke, M., Meijering, R., Schnorr, S., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., van de Sande, L., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Dupon, M., Gaborieau, V., Lacoste, D., Malvy, D., Mercie, P., Neau, D., Pellegrin, L. J., Tchamgoue, S., Lazaro, E., Cazanave, C., Vandenhende, M., Vareil, O. M., Gerard, Y., Blanco, P., Bouchet, S., Breilh, D., Fleury, H., Pellegrin, I., Chene, G., Thiebaut, R., Wittkop, L., Lawson-Ayayi, S., Gimbert, A., Desjardin, S., Lacaze-Buzy, L., Petrov-Sanchez, V., Andre, N., Bernard, K., Caubet, O., Caunegre, L., Chossat, I., Courtault, C., Dauchy, A. F., Dondia, D., Duffau, P., Dutronc, H., Farbos, S., Faure, I., Ferrand, H., Greib, C., Hessamfar, M., Imbert, Y., Lataste, P., Marie, J., Mechain, M., Monlun, E., Ochoa, A., Pistone, T., Raymond, I., Receveur, C. M., Rispal, P., Sorin, L., Valette, C., Viallard, J. F., Wille, H., Wirth, G., Lafon, M., Trimoulet, P., Bellecave, P., Tumiotto, C., Haramburu, F., Miremeont-Salame, G., Blaizeau, J. M., Decoin, M., Hannapier, C., Lenaud, E., Pougetoux, A., Delveaux, S., D'Ivernois, C., Diarra, F., Uwamaliya-Nziyumvira, B., Palmer, G., Conte, V., Sapparrart, V., Moore, R., Edwards, S., Hoy, J., Watson, K., Roth, N., Lau, H., Bloch, M., Baker, D., Carr, A., Cooper, D., O'Sullivan, M., Nolan, D., Guelfi, G., Domingo, P., Sambeat, A. M., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaque, A., Clumeck, N., Gennotte, F. A., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, C. M., Semaille, P., Van Laethem, Y., Neaton, J., El-Sadr, M. W., Krum, E., Thompson, G., Wentworth, D., Luskin-Hawk, R., Telzak, E., Abrams, I. D., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, R. L., Sampson, J., Baxter, J., Gazzard, B., Horban, A., Karpov, I., Pedersen, C., Ristola, M., Rockstroh, J., Peters, L., Fischer, H. A., Larsen, F. J., Podlekareva, D., Cozzi-Lepri, A., Shepherd, L., Schultze, A., Amele, S., Losso, M., Kundro, M., Schmied, B., Zangerle, R., Vassilenko, A., Mitsura, M. V., Paduto, D., Florence, E., Vandekerckhove, L., Hadziosmanovic, V., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Gerstoft, J., Katzenstein, T., Moller, F. N., Ostergaard, L., Wiese, L., Nielsen, N. L., Zilmer, K., Smidt, J., Aho, I., Viard, J. P., Girard, P. M., Duvivier, C., Schmidt, R., Degen, O., Stellbrink, J. H., Stefan, C., Bogner, J., Chkhartishvili, N., Gargalianos, P., Xylomenos, G., Armenis, K., Sambatakou, H., Szlavik, J., Gottfredsson, M., Mulcahy, F., Yust, I., Turner, D., Burke, M., Shahar, E., Hassoun, G., Elinav, H., Haouzi, M., Elbirt, D., Sthoeger, M. Z., Esposito, R., Mazeu, I., Mussini, C., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Zaccarelli, M., Antinori, A., Acinapura, R., Plazzi, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Uzdaviniene, V., Matulionyte, R., Staub, T., Hemmer, R., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Inglot, M., Bakowska, E., Flisiak, R., Grzeszczuk, A., Parczewski, M., Maciejewska, K., Aksak-Was, B., Beniowski, M., Mularska, E., Smiatacz, T., Gensing, M., Jablonowska, E., Malolepsza, E., Wojcik, K., Mozer-Lisewska, I., Caldeira, L., Mansinho, K., Maltez, F., Radoi, R., Oprea, C., Panteleev, A., Panteleev, O., Yakovlev, A., Trofimora, T., Khromova, I., Kuzovatova, E., Borodulina, E., Vdoushkina, E., Jevtovic, D., Tomazic, J., Miro, M. J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Gutierrez, M., Mateo, G., Laporte, M. J., Falconer, K., Thalme, A., Sonnerborg, A., Blaxhult, A., Flamholc, L., Cavassini, M., Calmy, A., Furrer, H., Battegay, M., Schmid, P., Kuznetsova, A., Kyselyova, G., Sluzhynska, M., Johnson, A. M., Simons, E., Orkin, C., Weber, J., Scullard, G., Clarke, A., Leen, C., Thulin, G., Akerlund, B., Koppel, K., Karlsson, A., Hakangard, C., Castelli, F., Cauda, R., Di Perri, G., Iardino, R., Ippolito, G., Marchetti, C. G., Perno, F. C., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Bonora, S., Borderi, M., Calcagno, A., Calza, L., Capobianchi, R. M., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Galli, L., Lorenzini, P., Rodano, A., Shanyinde, M., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petrone, F., Prota, G., Quartu, S., Truffa, S., Giacometti, A., Costantini, A., Barocci, V., Angarano, G., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, E. P., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Pan, A., Lorenzotti, S., Sighinolfi, L., Segala, D., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Milini, P., Rizzardini, G., Moioli, C. M., Piolini, R., Ridolfo, L. A., Salpietro, S., Tincati, C., Puzzolante, C., Abrescia, N., Chirianni, A., Borgia, G., Orlando, R., Bonadies, G., Di Martino, F., Gentile, I., Maddaloni, L., Cattelan, M. A., Marinello, S., Cascio, A., Colomba, C., Baldelli, F., Schiaroli, E., Parruti, G., Sozio, F., Magnani, G., Ursitti, A. M., Cristaudo, A., Baldin, G., Capozzi, M., Cicalini, S., Fontanelli Sulekova, L., Iaiani, G., Latini, A., Mastrorosa, I., Savinelli, S., Vergori, A., Cecchetto, M., Viviani, F., Bagella, P., Rossetti, B., Franco, A., Fontana Del Vecchio, R., Francisci, D., Di Giuli, C., Caramello, P., Orofino, C. G., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Starnini, G., Ialungo, A., Dellamonica, P., Bernard, E., Courjon, J., Cua, E., De Salvador-Guillouet, F., Durant, J., Etienne, C., Ferrando, S., Mondain-Miton, V., Naqvi, A., Perbost, I., Pillet, S., Prouvost-Keller, B., Pugliese, P., Rio, V., Risso, K., Roger, M. P., Aubert, V., Bernasconi, E., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Gunthard, F. H., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, D. R., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, J. K., Muller, N., Nicca, D., Pantaleo, G., Paioni, P., Rauch, A., Rudin, C., Speck, R., Stockle, M., Tarr, P., Trkola, A., Vernazza, P., Wandeler, G., Yerly, S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Chammartin F., Lodi S., Logan R., Ryom L., Mocroft A., Kirk O., D'Arminio Monforte A., Reiss P., Phillips A., El-Sadr W., Hatleberg C.I., Pradier C., Bonnet F., Law M., De Wit S., Sabin C., Lundgren J.D., Bucher H.C., Calvo G., Dabis F., Morfeldt L., Weber R., Lind-Thomsen A., Salbol Brandt R., Hillebreght M., Zaheri S., Wit F.W.N.M., Scherrer A., Schoni-Affolter F., Rickenbach M., Tavelli A., Fanti I., Leleux O., Mourali J., Le Marec F., Boerg E., Thulin E., Sundstrom A., Bartsch G., Thompsen G., Necsoi C., Delforge M., Fontas E., Caissotti C., Dollet K., Mateu S., Torres F., Petoumenos K., Blance A., Huang R., Puhr R., Gronborg Laut K., Kristensen D., Kamara D.A., Smith C.J., Raben D., Matthews C., Bojesen A., Grevsen A.L., Powderly B., Shortman N., Moecklinghoff C., Reilly G., Smit C., Ross M., Fux C.A., Morlat P., Friis-Moller N., Kowalska J., Bohlius J., Bower M., Fatkenheuer G., Grulich A., Sjol A., Meidahl P., Iversen J.S., Hillebregt M., Prins J.M., Kuijpers T.W., Scherpbier H.J., Van Der Meer J.T.M., Godfried M.H., Van Der Poll T., Nellen F.J.B., Geerlings S.E., Van Vugt M., Pajkrt D., Bos J.C., Wiersinga W.J., Van Der Valk M., Goorhuis A., Hovius J.W., Van Eden J., Henderiks A., Van Hes A.M.H., Mutschelknauss M., Nobel H.E., Pijnappel F.J.J., Jurriaans S., Back N.K.T., Zaaijer H.L., Berkhout B., Cornelissen M.T.E., Schinkel C.J., Thomas X.V., Van Den Berge M., Stegeman A., Baas S., Hage De Looff L., Versteeg D., Pronk M.J.H., Ammerlaan H.S.M., de Munnik E.S., Jansz A.R., Tjhie J., Wegdam M.C.A., Deiman B., Scharnhorst V., Van Der Plas A., Weijsenfeld A.M., Van Der Ende M.E., de Vries-Sluijs T.E.M.S., van Gorp E.C.M., Schurink C.A.M., Nouwen J.L., Verbon A., Rijnders B.J.A., Bax H.I., Van Der Feltz M., Bassant N., Van Beek J.E.A., Vriesde M., Van Zonneveld L.M., De Oude-Lubbers A., Van Den Berg-Cameron H.J., Bruinsma-Broekman F.B., de Groot J., De Zeeuw-De Man M., Boucher C.A.B., Koopmans M.P.G., van Kampen J.J.A., Pas S.D., Driessen G.J.A., van Rossum A.M.C., Van Der Knaap L.C., Visser E., Branger J., Rijkeboer-Mes A., Duijf-Van De Ven C.J.H.M., Schippers E.F., van Nieuwkoop C., van IJperen J.M., Geilings J., van der Hut G., Franck P.F.H., Van Eeden A., Brokking W., Groot M., Elsenburg L.J.M., Damen M., Kwa I.S., Groeneveld P.H.P., Bouwhuis J.W., Van Den Berg J.F., Van Hulzen A.G.W., Van Der Bliek G.L., Bor P.C.J., Bloembergen P., Wolfhagen M.J.H.M., Ruijs G.J.H.M., Kroon F.P., De Boer M.G.J., Bauer M.P., Jolink H., Vollaard A.M., Dorama W., Van Holten N., Claas E.C.J., Wessels E., Den Hollander J.G., Pogany K., Roukens A., Kastelijns M., Smit J.V., Smit E., Struik-Kalkman D., Tearno C., Bezemer M., van Niekerk T., Pontesilli O., Lowe S.H., Oude Lashof A.M.L., Posthouwer D., Ackens R.P., Schippers J., Vergoossen R., Weijenberg-Maes B., van Loo I.H.M., Havenith T.R.A., Leyten E.M.S., Gelinck L.B.S., van Hartingsveld A., Meerkerk C., Wildenbeest G.S., Mutsaers J.A.E.M., Jansen C.L., Mulder J.W., Vrouenraets S.M.E., Lauw F.N., van Broekhuizen M.C., Paap H., Vlasblom D.J., Smits P.H.M., Weijer S., El Moussaoui R., Bosma A.S., van Vonderen M.G.A., van Houte D.P.F., Kampschreur L.M., Dijkstra K., Faber S., Weel J., Kootstra G.J., Delsing C.E., van der Burg-Van de Plas M., Heins H., Lucas E., Kortmann W., van Twillert G., Cohen Stuart J.W.T., Diederen B.M.W., van Truijen-Oud F.A., van der Reijden W.A., Jansen R., Brinkman K., van den Berk G.E.L., Blok W.L., Frissen P.H.J., Lettinga K.D., Schouten W.E.M., Veenstra J., Brouwer J.C., Geerders F.G., Hoeksema K., Kleene J.M., van der Meche B.I., Spelbrink M., Sulman H., Toonen A.J.M., Wijnands S., Kwa D., Witte E., Koopmans P.P., Keuter M., van der Ven A.J.A.M., ter Hofstede H.J.M., Dofferhoff A.S.M., van Crevel R., Albers M., Bosch M.E.W., Grintjes-Huisman K.J.T., Zomer J.B., Stelma F.F., Rahamat-Langendoen J., Burger D., Richter C., Gisolf H.E., Hassing J.R., ter Beest G., van Bentum P.H.M., Langebeek N., Tiemessen R., Swanink C.M.A., van Lelyveld S.F.L., Soetekouw R., Hulshoff N., van der Prijt L.M.M., van der Swaluw J., Bermon N., Herpers B.L., Veenendaal D., Verhagen W.D.M., van Wijk M., van Kasteren M.E.E., Brouwer E.A., de Kruijf-Van de Wiel B.A.F.M., Kuipers M., Santegoets R.M.W.J., van der Ven B., Marcelis H.J., Buiting A.G.M., Kabel J.P., Bierman W.F.W., Scholvinck H., Wilting R.K., Stienstra Y., de Groot-De Jonge H., van der Meulen A.P., de Weerd A.D., Ludwig-Roukema J., Niesters H.G.M., Riezebos-Brilman A., van Leer-Buter C.C., Knoester M., Hoepelman A.I.M., Mudrikova T., Ellerbroek M.P., Oosterheert J.J., Arends E.J., Barth E.R., Wassenberg M.W.M., Schadd M.E., van Elst-Laurijssen D.H.M., van Oers-Hazelzet B.E., Vervoort S., van Berkel M., Schuurman R., Verduyn-Lunel F., Wensing A.M.J., Peters E.J.G., van Agtmael A.M., Bomers M., de Vocht J., Heitmuller M., Laan M.L., Pettersson M.A., Vandenbroucke-Grauls C.M.J.E., Ang W.C., Geelen S.P.M., Wolfs T.F.W., Bont J.L., Nauta N., Bezemer O.D., van Sighem I.A., Boender S.T., de Jong A., Bergsma D., Hoekstra P., de Lang A., Grivell S., Jansen A., Rademaker J.M., Raethke M., Meijering R., Schnorr S., de Groot L., van den Akker M., Bakker Y., Claessen E., El Berkaoui A., Koops J., Kruijne E., Lodewijk C., Munjishvili L., Peeck B., Ree C., Regtop R., Ruijs Y., Rutkens T., van de Sande L., Schoorl M., Timmerman A., Tuijn E., Veenenberg L., van der Vliet S., Wisse A., Woudstra T., Tuk B., Dupon M., Gaborieau V., Lacoste D., Malvy D., Mercie P., Neau D., Pellegrin L.J., Tchamgoue S., Lazaro E., Cazanave C., Vandenhende M., Vareil O.M., Gerard Y., Blanco P., Bouchet S., Breilh D., Fleury H., Pellegrin I., Chene G., Thiebaut R., Wittkop L., Lawson-Ayayi S., Gimbert A., Desjardin S., Lacaze-Buzy L., Petrov-Sanchez V., Andre N., Bernard K., Caubet O., Caunegre L., Chossat I., Courtault C., Dauchy A.F., Dondia D., Duffau P., Dutronc H., Farbos S., Faure I., Ferrand H., Greib C., Hessamfar M., Imbert Y., Lataste P., Marie J., Mechain M., Monlun E., Ochoa A., Pistone T., Raymond I., Receveur C.M., Rispal P., Sorin L., Valette C., Viallard J.F., Wille H., Wirth G., Lafon M., Trimoulet P., Bellecave P., Tumiotto C., Haramburu F., Miremeont-Salame G., Blaizeau J.M., Decoin M., Hannapier C., Lenaud E., Pougetoux A., Delveaux S., D'Ivernois C., Diarra F., Uwamaliya-Nziyumvira B., Palmer G., Conte V., Sapparrart V., Moore R., Edwards S., Hoy J., Watson K., Roth N., Lau H., Bloch M., Baker D., Carr A., Cooper D., O'Sullivan M., Nolan D., Guelfi G., Domingo P., Sambeat A.M., Gatell J., Del Cacho E., Cadafalch J., Fuster M., Codina C., Sirera G., Vaque A., Clumeck N., Gennotte F.A., Gerard M., Kabeya K., Konopnicki D., Libois A., Martin C., Payen C.M., Semaille P., Van Laethem Y., Neaton J., El-Sadr M.W., Krum E., Thompson G., Wentworth D., Luskin-Hawk R., Telzak E., Abrams I.D., Cohn D., Markowitz N., Arduino R., Mushatt D., Friedland G., Perez G., Tedaldi E., Fisher E., Gordin F., Crane R.L., Sampson J., Baxter J., Gazzard B., Horban A., Karpov I., Pedersen C., Ristola M., Rockstroh J., Peters L., Fischer H.A., Larsen F.J., Podlekareva D., Cozzi-Lepri A., Shepherd L., Schultze A., Amele S., Losso M., Kundro M., Schmied B., Zangerle R., Vassilenko A., Mitsura M.V., Paduto D., Florence E., Vandekerckhove L., Hadziosmanovic V., Begovac J., Machala L., Jilich D., Sedlacek D., Kronborg G., Benfield T., Gerstoft J., Katzenstein T., Moller F.N., Ostergaard L., Wiese L., Nielsen N.L., Zilmer K., Smidt J., Aho I., Viard J.P., Girard P.M., Duvivier C., Schmidt R., Degen O., Stellbrink J.H., Stefan C., Bogner J., Chkhartishvili N., Gargalianos P., Xylomenos G., Armenis K., Sambatakou H., Szlavik J., Gottfredsson M., Mulcahy F., Yust I., Turner D., Burke M., Shahar E., Hassoun G., Elinav H., Haouzi M., Elbirt D., Sthoeger M.Z., Esposito R., Mazeu I., Mussini C., Mazzotta F., Gabbuti A., Vullo V., Lichtner M., Zaccarelli M., Antinori A., Acinapura R., Plazzi M., Lazzarin A., Castagna A., Gianotti N., Galli M., Ridolfo A., Rozentale B., Uzdaviniene V., Matulionyte R., Staub T., Hemmer R., Ormaasen V., Maeland A., Bruun J., Knysz B., Gasiorowski J., Inglot M., Bakowska E., Flisiak R., Grzeszczuk A., Parczewski M., Maciejewska K., Aksak-Was B., Beniowski M., Mularska E., Smiatacz T., Gensing M., Jablonowska E., Malolepsza E., Wojcik K., Mozer-Lisewska I., Caldeira L., Mansinho K., Maltez F., Radoi R., Oprea C., Panteleev A., Panteleev O., Yakovlev A., Trofimora T., Khromova I., Kuzovatova E., Borodulina E., Vdoushkina E., Jevtovic D., Tomazic J., Miro M.J., Moreno S., Rodriguez J.M., Clotet B., Jou A., Paredes R., Tural C., Puig J., Bravo I., Gutierrez M., Mateo G., Laporte M.J., Falconer K., Thalme A., Sonnerborg A., Blaxhult A., Flamholc L., Cavassini M., Calmy A., Furrer H., Battegay M., Schmid P., Kuznetsova A., Kyselyova G., Sluzhynska M., Johnson A.M., Simons E., Orkin C., Weber J., Scullard G., Clarke A., Leen C., Thulin G., Akerlund B., Koppel K., Karlsson A., Hakangard C., Castelli F., Cauda R., Di Perri G., Iardino R., Ippolito G., Marchetti C.G., Perno F.C., von Schloesser F., Viale P., Ceccherini-Silberstein F., Girardi E., Lo Caputo S., Puoti M., Andreoni M., Ammassari A., Balotta C., Bandera A., Bonfanti P., Bonora S., Borderi M., Calcagno A., Calza L., Capobianchi R.M., Cingolani A., Cinque P., De Luca A., Di Biagio A., Gori A., Guaraldi G., Lapadula G., Madeddu G., Maggiolo F., Marcotullio S., Monno L., Nozza S., Quiros Roldan E., Rossotti R., Rusconi S., Santoro M.M., Saracino A., Galli L., Lorenzini P., Rodano A., Shanyinde M., Carletti F., Carrara S., Di Caro A., Graziano S., Petrone F., Prota G., Quartu S., Truffa S., Giacometti A., Costantini A., Barocci V., Angarano G., Santoro C., Suardi C., Donati V., Verucchi G., Minardi C., Quirino T., Abeli C., Manconi E.P., Piano P., Cacopardo B., Celesia B., Vecchiet J., Falasca K., Pan A., Lorenzotti S., Sighinolfi L., Segala D., Vichi F., Cassola G., Viscoli C., Alessandrini A., Bobbio N., Mazzarello G., Mastroianni C., Belvisi V., Caramma I., Chiodera A., Milini P., Rizzardini G., Moioli C.M., Piolini R., Ridolfo L.A., Salpietro S., Tincati C., Puzzolante C., Abrescia N., Chirianni A., Borgia G., Orlando R., Bonadies G., Di Martino F., Gentile I., Maddaloni L., Cattelan M.A., Marinello S., Cascio A., Colomba C., Baldelli F., Schiaroli E., Parruti G., Sozio F., Magnani G., Ursitti A.M., Cristaudo A., Baldin G., Capozzi M., Cicalini S., Fontanelli Sulekova L., Iaiani G., Latini A., Mastrorosa I., Savinelli S., Vergori A., Cecchetto M., Viviani F., Bagella P., Rossetti B., Franco A., Fontana Del Vecchio R., Francisci D., Di Giuli C., Caramello P., Orofino C.G., Sciandra M., Bassetti M., Londero A., Pellizzer G., Manfrin V., Starnini G., Ialungo A., Dellamonica P., Bernard E., Courjon J., Cua E., De Salvador-Guillouet F., Durant J., Etienne C., Ferrando S., Mondain-Miton V., Naqvi A., Perbost I., Pillet S., Prouvost-Keller B., Pugliese P., Rio V., Risso K., Roger M.P., Aubert V., Bernasconi E., Ciuffi A., Dollenmaier G., Egger M., Elzi L., Fehr J., Fellay J., Gunthard F.H., Haerry D., Hasse B., Hirsch H.H., Hoffmann M., Hosli I., Kahlert C., Kaiser L., Keiser O., Klimkait T., Kouyos D.R., Kovari H., Ledergerber B., Martinetti G., Martinez de Tejada B., Marzolini C., Metzner J.K., Muller N., Nicca D., Pantaleo G., Paioni P., Rauch A., Rudin C., Speck R., Stockle M., Tarr P., Trkola A., Vernazza P., Wandeler G., Yerly S., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Internal Medicine, Medical Microbiology & Infectious Diseases, Virology, Pediatric Surgery, Pediatrics, Chammartin, F, Lodi, S, Logan, R, Ryom, L, Mocroft, A, Kirk, O, D'Arminio Monforte, A, Reiss, P, Phillips, A, El-Sadr, W, Hatleberg, C, Pradier, C, Bonnet, F, Law, M, De Wit, S, Sabin, C, Lundgren, J, Bucher, H, Calvo, G, Dabis, F, Morfeldt, L, Weber, R, Lind-Thomsen, A, Salbol Brandt, R, Hillebreght, M, Zaheri, S, Wit, F, Scherrer, A, Schoni-Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundstrom, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Dollet, K, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Gronborg Laut, K, Kristensen, D, Kamara, D, Smith, C, Raben, D, Matthews, C, Bojesen, A, Grevsen, A, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Smit, C, Ross, M, Fux, C, Morlat, P, Friis-Moller, N, Kowalska, J, Bohlius, J, Bower, M, Fatkenheuer, G, Grulich, A, Sjol, A, Meidahl, P, Iversen, J, Hillebregt, M, Prins, J, Kuijpers, T, Scherpbier, H, Van Der Meer, J, Godfried, M, Van Der Poll, T, Nellen, F, Geerlings, S, Van Vugt, M, Pajkrt, D, Bos, J, Wiersinga, W, Van Der Valk, M, Goorhuis, A, Hovius, J, Van Eden, J, Henderiks, A, Van Hes, A, Mutschelknauss, M, Nobel, H, Pijnappel, F, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Thomas, X, Van Den Berge, M, Stegeman, A, Baas, S, Hage De Looff, L, Versteeg, D, Pronk, M, Ammerlaan, H, de Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, Van Der Plas, A, Weijsenfeld, A, Van Der Ende, M, de Vries-Sluijs, T, van Gorp, E, Schurink, C, Nouwen, J, Verbon, A, Rijnders, B, Bax, H, Van Der Feltz, M, Bassant, N, Van Beek, J, Vriesde, M, Van Zonneveld, L, De Oude-Lubbers, A, Van Den Berg-Cameron, H, Bruinsma-Broekman, F, de Groot, J, De Zeeuw-De Man, M, Boucher, C, Koopmans, M, van Kampen, J, Pas, S, Driessen, G, van Rossum, A, Van Der Knaap, L, Visser, E, Branger, J, Rijkeboer-Mes, A, Duijf-Van De Ven, C, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, Franck, P, Van Eeden, A, Brokking, W, Groot, M, Elsenburg, L, Damen, M, Kwa, I, Groeneveld, P, Bouwhuis, J, Van Den Berg, J, Van Hulzen, A, Van Der Bliek, G, Bor, P, Bloembergen, P, Wolfhagen, M, Ruijs, G, Kroon, F, De Boer, M, Bauer, M, Jolink, H, Vollaard, A, Dorama, W, Van Holten, N, Claas, E, Wessels, E, Den Hollander, J, Pogany, K, Roukens, A, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, Bezemer, M, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Schippers, J, Vergoossen, R, Weijenberg-Maes, B, van Loo, I, Havenith, T, Leyten, E, Gelinck, L, van Hartingsveld, A, Meerkerk, C, Wildenbeest, G, Mutsaers, J, Jansen, C, Mulder, J, Vrouenraets, S, Lauw, F, van Broekhuizen, M, Paap, H, Vlasblom, D, Smits, P, Weijer, S, El Moussaoui, R, Bosma, A, van Vonderen, M, van Houte, D, Kampschreur, L, Dijkstra, K, Faber, S, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Lucas, E, Kortmann, W, van Twillert, G, Cohen Stuart, J, Diederen, B, van Truijen-Oud, F, van der Reijden, W, Jansen, R, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Brouwer, J, Geerders, F, Hoeksema, K, Kleene, J, van der Meche, B, Spelbrink, M, Sulman, H, Toonen, A, Wijnands, S, Kwa, D, Witte, E, Koopmans, P, Keuter, M, van der Ven, A, ter Hofstede, H, Dofferhoff, A, van Crevel, R, Albers, M, Bosch, M, Grintjes-Huisman, K, Zomer, J, Stelma, F, Rahamat-Langendoen, J, Burger, D, Richter, C, Gisolf, H, Hassing, J, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, Hulshoff, N, van der Prijt, L, van der Swaluw, J, Bermon, N, Herpers, B, Veenendaal, D, Verhagen, W, van Wijk, M, van Kasteren, M, Brouwer, E, de Kruijf-Van de Wiel, B, Kuipers, M, Santegoets, R, van der Ven, B, Marcelis, H, Buiting, A, Kabel, J, Bierman, W, Scholvinck, H, Wilting, R, Stienstra, Y, de Groot-De Jonge, H, van der Meulen, A, de Weerd, A, Ludwig-Roukema, J, Niesters, H, Riezebos-Brilman, A, van Leer-Buter, C, Knoester, M, Hoepelman, A, Mudrikova, T, Ellerbroek, M, Oosterheert, J, Arends, E, Barth, E, Wassenberg, M, Schadd, M, van Elst-Laurijssen, D, van Oers-Hazelzet, B, Vervoort, S, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Peters, E, van Agtmael, A, Bomers, M, de Vocht, J, Heitmuller, M, Laan, M, Pettersson, M, Vandenbroucke-Grauls, C, Ang, W, Geelen, S, Wolfs, T, Bont, J, Nauta, N, Bezemer, O, van Sighem, I, Boender, S, de Jong, A, Bergsma, D, Hoekstra, P, de Lang, A, Grivell, S, Jansen, A, Rademaker, J, Raethke, M, Meijering, R, Schnorr, S, de Groot, L, van den Akker, M, Bakker, Y, Claessen, E, El Berkaoui, A, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, van de Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, van der Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercie, P, Neau, D, Pellegrin, L, Tchamgoue, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, O, 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Sirera, G, Vaque, A, Clumeck, N, Gennotte, F, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, C, Semaille, P, Van Laethem, Y, Neaton, J, El-Sadr, M, Krum, E, Thompson, G, Wentworth, D, Luskin-Hawk, R, Telzak, E, Abrams, I, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, R, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Pedersen, C, Ristola, M, Rockstroh, J, Peters, L, Fischer, H, Larsen, F, Podlekareva, D, Cozzi-Lepri, A, Shepherd, L, Schultze, A, Amele, S, Losso, M, Kundro, M, Schmied, B, Zangerle, R, Vassilenko, A, Mitsura, M, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Sedlacek, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Moller, F, Ostergaard, L, Wiese, L, Nielsen, N, Zilmer, K, Smidt, J, Aho, I, Viard, J, Girard, P, Duvivier, C, Schmidt, R, Degen, O, Stellbrink, J, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Xylomenos, G, Armenis, K, Sambatakou, H, Szlavik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, M, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Matulionyte, R, Staub, T, Hemmer, R, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak-Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer-Lisewska, I, Caldeira, L, Mansinho, K, Maltez, F, Radoi, R, Oprea, C, Panteleev, A, Panteleev, O, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Miro, M, Moreno, S, Rodriguez, J, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, M, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Battegay, M, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, A, Simons, E, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Akerlund, B, Koppel, K, Karlsson, A, Hakangard, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, C, Perno, F, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, R, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marcotullio, S, Monno, L, Nozza, S, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, E, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, C, Piolini, R, Ridolfo, L, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, M, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, A, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Fontanelli Sulekova, L, Iaiani, G, Latini, A, Mastrorosa, I, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Fontana Del Vecchio, R, Francisci, D, Di Giuli, C, Caramello, P, Orofino, C, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador-Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain-Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost-Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, M, Aubert, V, Bernasconi, E, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Gunthard, F, Haerry, D, Hasse, B, Hirsch, H, Hoffmann, M, Hosli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, D, Kovari, H, Ledergerber, B, Martinetti, G, Martinez de Tejada, B, Marzolini, C, Metzner, J, Muller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Speck, R, Stockle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, Yerly, S, Internal medicine, Pediatric surgery, Medical Microbiology and Infection Prevention, Amsterdam Gastroenterology Endocrinology Metabolism, Faculteit Medische Wetenschappen/UMCG, Microbes in Health and Disease (MHD), and Molecular Pharmacology

Subjects
Male, HIV AIDS, HIV Infections, 0302 clinical medicine, Interquartile range, Risk Factors, Neoplasms, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, 0303 health sciences, Incidence, Absolute risk reduction, Drugs, General Medicine, Middle Aged, Viral Load, Antiretroviral therapy, 3. Good health, AIDS, Cancer treatment, Prevention policy and public health, Cohort, Infectious diseases, Cohort studies, Female, Viral load, Adult, medicine.medical_specialty, Anti-HIV Agents, HIV Infections/drug therapy, Socio-culturale, Time-to-Treatment, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, Internal Medicine, Humans, Adverse effect, 030306 microbiology, business.industry, HIV, Cancer, medicine.disease, CD4 Lymphocyte Count, Anti-HIV Agents/therapeutic use, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Neoplasms/epidemiology
Abstract

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10 9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy.DESIGN: Multinational prospective cohort study.SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 10 9 cells/L and less than 350 × 10 9 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design.CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Published
2021
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41. Efficacy and safety of IV ferumoxytol for iron deficiency anemia in patients with cancer

Author

Vadhan-Raj S, Dahl NV, Bernard K, Li Z, and Strauss WE

Subjects
anemia, cancer, ferumoxytol, hemoglobin, efficacy, intravenous iron, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Saroj Vadhan-Raj,1 Naomi V Dahl,2 Kristine Bernard,2 Zhu Li,2 William E Strauss2 1Division of Cancer Medicine, University of Texas, MD Anderson Cancer Center, Houston, TX, USA; 2AMAG Pharmaceuticals, Inc., Waltham, MA, USA Purpose: Iron deficiency anemia (IDA) is common in cancer patients due to blood loss and inflammation. Many do not tolerate oral iron or adequately respond. Intravenous (IV) iron is commonly used as an adjunct to erythropoiesis-stimulating agents; data on the use of IV iron monotherapy in these patients are limited. This study aimed to evaluate IV ferumoxytol for the treatment of cancer patients with IDA with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Patients and methods: This post hoc analysis of pooled data from two multicenter, randomized, controlled, Phase III trials evaluating IV ferumoxytol (510 mg ×2) vs placebo or iron sucrose (200 mg ×5) included a subgroup of 98 patients with cancer that the investigator identified as the primary cause of their IDA, or with cancer whose IDA was attributed to another comorbid condition (ferumoxytol, n=75; iron sucrose, n=13; placebo, n=10). Gastrointestinal cancers were most common (42), followed by breast (14), cervix (ten), and lung (nine). The primary endpoint was the mean change in hemoglobin (Hgb) from baseline to week 5. Results: At week 5, both ferumoxytol and iron sucrose produced significant increases in Hgb from baseline (1.8 g/dL [P20% nor initiated in any treatment group. Overall rates of adverse events and serious adverse events in the cancer subgroup mirrored those in the overall study population. Conclusion: Monotherapy with IV iron appears to be an effective option for cancer patients with IDA who do not respond to or cannot tolerate oral iron therapy. Keywords: anemia, cancer, ferumoxytol, hemoglobin, efficacy, intravenous iron

Published
2017

42. Comparative safety of intravenous Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia: rationale and study design of a randomized double-blind study with a focus on acute hypersensitivity reactions

Author

Adkinson NF, Strauss WE, Bernard K, Kaper RF, Macdougall IC, and Krop JS

Subjects
anaphylaxis, ferric carboxymaltose, ferumoxytol, hypersensitivity, hypotension, iron deficiency anemia, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

N Franklin Adkinson,1 William E Strauss,2 Kristine Bernard,2 Robert F Kaper,2 Iain C Macdougall,3 Julie S Krop2 1Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2AMAG Pharmaceuticals, Inc., Waltham, MA, USA; 3Department of Renal Medicine, King’s College Hospital, London, UK Background: Intravenous (IV) iron is often used to treat iron deficiency anemia in patients who are unable to tolerate or are inadequately managed with oral iron. However, IV iron treatment has been associated with acute hypersensitivity reactions. The comparative risk of adverse events (AEs) with IV iron preparations has been assessed by a few randomized controlled trials, which are most often limited by small patient numbers, which lack statistical power to identify differences in low-frequency AE such as hypersensitivity reactions.Materials and methods: Ferumoxytol versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia (FIRM) is a randomized, double-blind, international, multicenter, Phase III study designed to compare the safety of ferumoxytol and ferric carboxymaltose (FCM). The study includes adults with hemoglobin

Published
2017

46. Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA:a phase 2 randomized clinical trial

Author

Schnitzer, T., Pueyo, M., Deckx, H., van der Aar, E., Bernard, K., Hatch, S., van der Stoep, M., Grankov, S., Phung, D., Imbert, O., Chimits, D., Muller, K., Hochberg, M. C., Bliddal, H., Wirth, W., Eckstein, F., Conaghan, P. G., Schnitzer, T., Pueyo, M., Deckx, H., van der Aar, E., Bernard, K., Hatch, S., van der Stoep, M., Grankov, S., Phung, D., Imbert, O., Chimits, D., Muller, K., Hochberg, M. C., Bliddal, H., Wirth, W., Eckstein, F., and Conaghan, P. G.

Abstract

Objective: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. Design: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40–75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren–Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. Results: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. Conclusions: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

Published
2023

47. Micro-Topographies Induce Epigenetic Reprogramming and Quiescence in Human Mesenchymal Stem Cells

Author

Vermeulen, Steven, Van Puyvelde, Bart, Bengtsson del Barrio, Laura, Almey, Ruben, van der Veer, Bernard K., Deforce, Dieter, Dhaenens, Maarten, de Boer, Jan, Vermeulen, Steven, Van Puyvelde, Bart, Bengtsson del Barrio, Laura, Almey, Ruben, van der Veer, Bernard K., Deforce, Dieter, Dhaenens, Maarten, and de Boer, Jan

Abstract

Biomaterials can control cell and nuclear morphology. Since the shape of the nucleus influences chromatin architecture, gene expression and cell identity, surface topography can control cell phenotype. This study provides fundamental insights into how surface topography influences nuclear morphology, histone modifications, and expression of histone-associated proteins through advanced histone mass spectrometry and microarray analysis. The authors find that nuclear confinement is associated with a loss of histone acetylation and nucleoli abundance, while pathway analysis reveals a substantial reduction in gene expression associated with chromosome organization. In light of previous observations where the authors found a decrease in proliferation and metabolism induced by micro-topographies, they connect these findings with a quiescent phenotype in mesenchymal stem cells, as further shown by a reduction of ribosomal proteins and the maintenance of multipotency on micro-topographies after long-term culture conditions. Also, this influence of micro-topographies on nuclear morphology and proliferation is reversible, as shown by a return of proliferation when re-cultured on a flat surface. The findings provide novel insights into how biophysical signaling influences the epigenetic landscape and subsequent cellular phenotype.

Published
2023

48. Osmolar Modulation Drives Reversible Cell Cycle Exit and Human Pluripotent Cell Differentiation via NF‐κВ and WNT Signaling.

Author

Chui, Jonathan Sai‐Hong, Izuel‐Idoype, Teresa, Qualizza, Alessandra, de Almeida, Rita Pires, Piessens, Lindsey, van der Veer, Bernard K., Vanmarcke, Gert, Malesa, Aneta, Athanasouli, Paraskevi, Boon, Ruben, Vriens, Joris, van Grunsven, Leo, Koh, Kian Peng, Verfaillie, Catherine M., and Lluis, Frederic

Subjects
HUMAN cell cycle, WNT signal transduction, CELL differentiation, CELL cycle, PLURIPOTENT stem cells, GROWTH
Abstract

Terminally differentiated cells are commonly regarded as the most stable cell state in adult organisms, characterized by growth arrest while fulfilling their specialized functions. A better understanding of the mechanisms involved in promoting cell cycle exit will improve the ability to differentiate pluripotent cells into mature tissues for both pharmacological and therapeutic use. Here, it demonstrates that a hyperosmolar environment enforces a protective p53‐independent quiescent state in immature hepatoma cells and in pluripotent stem cell‐derived models of human hepatocytes and endothelial cells. Prolonged culture in hyperosmolar conditions stimulates changes in gene expression promoting functional cell maturation. Interestingly, hyperosmolar conditions do not only trigger growth arrest and cellular maturation but are also necessary to maintain this maturated state, as switching back to plasma osmolarity reverses the changes in expression of maturation and proliferative markers. Transcriptome analysis revealed sequential stages of osmolarity‐regulated growth arrest followed by cell maturation, mediated by activation of NF‐κВ, and repression of WNT signaling, respectively. This study reveals that a modulated increase in osmolarity serves as a biochemical signal to promote long‐term growth arrest and cellular maturation into different lineages, providing a practical method to generate differentiated hiPSCs that resemble their mature counterpart more closely. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Spatially Self‐Organized Three‐Dimensional Neural Concentroid as a Novel Reductionist Humanized Model to Study Neurovascular Development.

Author

Chai, Yoke Chin, To, San Kit, Simorgh, Susan, Zaunz, Samantha, Zhu, YingLi, Ahuja, Karan, Lemaitre, Alix, Ramezankhani, Roya, van der Veer, Bernard K., Wierda, Keimpe, Verhulst, Stefaan, van Grunsven, Leo A., Pasque, Vincent, and Verfaillie, Catherine

Subjects
PLURIPOTENT stem cells, HUMAN stem cells, NEURAL development, CELL migration, NEURONAL differentiation, FETAL brain
Abstract

Although human pluripotent stem cell (PSC)‐derived brain organoids have enabled researchers to gain insight into human brain development and disease, these organoids contain solely ectodermal cells and are not vascularized as occurs during brain development. Here it is created less complex and more homogenous large neural constructs starting from PSC‐derived neuroprogenitor cells (NPC), by fusing small NPC spheroids into so‐called concentroids. Such concentroids consisted of a pro‐angiogenic core, containing neuronal and outer radial glia cells, surrounded by an astroglia‐dense outer layer. Incorporating PSC‐derived endothelial cells (EC) around and/or in the concentroids promoted vascularization, accompanied by differential outgrowth and differentiation of neuronal and astroglia cells, as well as the development of ectodermal‐derived pericyte‐like mural cells co‐localizing with EC networks. Single nucleus transcriptomic analysis revealed an enhanced neural cell subtype maturation and diversity in EC‐containing concentroids, which better resemble the fetal human brain compared to classical organoids or NPC‐only concentroids. This PSC‐derived "vascularized" concentroid brain model will facilitate the study of neurovascular/blood‐brain barrier development, neural cell migration, and the development of effective in vitro vascularization strategies of brain mimics. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation

Author

van der Veer, Bernard K, primary, Chen, Lehua, additional, Custers, Colin, additional, Athanasouli, Paraskevi, additional, Schroiff, Mariana, additional, Cornelis, Riet, additional, Chui, Jonathan Sai-Hong, additional, Finnell, Richard H, additional, Lluis, Frederic, additional, and Koh, Kian Peng, additional

Published
2023
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