Author: "P Goulder" - Searchworks@Jio Institute Digital Library Search Results

631 results on '"P Goulder"'

1. Sustained aviremia despite anti-retroviral therapy non-adherence in male children after in utero HIV transmission

Author: Bengu, Nomonde, Cromhout, Gabriela, Adland, Emily, Govender, Katya, Herbert, Nicholas, Lim, Nicholas, Fillis, Rowena, Sprenger, Kenneth, Vieira, Vinicius, Kannie, Samantha, van Lobenstein, Jeroen, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Mchunu, Noxolo, Pascucci, Giuseppe Rubens, Cotugno, Nicola, Palma, Paolo, Tagarro, Alfredo, Rojo, Pablo, Roider, Julia, Garcia-Guerrero, Maria C., Ochsenbauer, Christina, Groll, Andreas, Reddy, Kavidha, Giaquinto, Carlo, Rossi, Paolo, Hong, Seohyun, Dong, Krista, Ansari, M. Azim, Puertas, Maria C., Ndung’u, Thumbi, Capparelli, Edmund, Lichterfeld, Mathias, Martinez-Picado, Javier, Kappes, John C., Archary, Moherndran, and Goulder, Philip
Published: 2024
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2. Unmet needs of highrisk mothers reduce success of antiretroviral treatment in HIVinfected infants

Author: Z Mvo, V Ntlantsana, N Bengu, J Millar, J Roider, R Bhoola, M Krishna, Y Graza, J van Lobenstein, C Kapongo, C Kogielambal, K Sprenger, M Archary, T Ndung'u, and P Goulder
Subjects: Medicine, Medicine (General), R5-920
Abstract: In the era of effective prevention of mother-to-child transmission of HIV, the same psychosocioeconomic factors that predispose to mother-to-child transmission also substantially increase the likelihood of antiretroviral therapy failure in infected infants. For HIV-infected infants to benefit from early infant diagnosis and treatment initiation, into which much funding and effort is now invested, it is vital that these unmet needs of high-risk mothers are urgently attended to. From an ongoing study of early infant diagnosis and treatment following in utero transmission in KwaZulu-Natal, South Africa, we describe four cases to highlight these challenges facing transmitting mothers that contribute to treatment failure in their infants.
Published: 2018
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3. Early learnings from UNICEF's work to employ gender transformative approaches to advance adolescent girls' rights

Author: Lauren Rumble, Suzanne Petroni, and Ruth Graham Goulder
Subjects: Adolescent girls, Child marriage, Protection, Skills, Learning, UNICEF, Social sciences (General), H1-99
Abstract: UNICEF policies, plans, and strategies increasingly demonstrate that gender equality and the empowerment of girls are central to the organization's mandate to advance child rights. In its newest frameworks, UNICEF has pledged to practice gender transformative approaches to achieve progress toward advancing adolescent girls' wellbeing and agency, as well as a more gender equal world. Employing such approaches requires shifting power and resources to adolescent girls and girl-led organizations and networks. This means deliberate support for girls' capacities as leaders and changemakers; understanding and confronting the gendered and age-related power dynamics and norms that impede gender equality at all levels of society and stages of life; and working with girls and their communities to create more gender equitable environments for girls' rights (Rumble et al., 2022).UNICEF has seen some early successes, but also encountered challenges in applying these approaches. Gaps in expertise, restricted funding, and political sensitivities are just a few impediments to ensuring transformative action at scale. Yet, the potential impacts are enormous.In this Practice Perspective Article, we share our reflections on principles UNICEF is applying, implementation challenges it is encountering, early outcomes it is capturing, and lessons it is learning in its work to employ gender-transformative approaches to further adolescent girls’ rights.
Published: 2024
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4. Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population

Author: Panagiota Zacharopoulou, Ming Lee, Thiago Oliveira, John Thornhill, Nicola Robinson, Helen Brown, Sabine Kinloch, Philip Goulder, Julie Fox, Sarah Fidler, M. Azim Ansari, and John Frater
Subjects: HIV - human immunodeficiency virus, primary HIV infection (PHI), broadly neutralising antibodies, 10-1074, resistance screening, Immunologic diseases. Allergy, RC581-607
Abstract: Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074. The prevalence of both de novo and emergent 10-1074 resistance will determine its use at a population level both to protect against HIV transmission and as an option for treatment. To help understand this further, we report the prevalence of pre-existing mutations associated with 10-1074 resistance in a bNAb-naive population of 157 individuals presenting to UK HIV centres with primary HIV infection, predominantly B clade, receiving antiretroviral treatment. Single genome analysis of HIV proviral envelope sequences showed that 29% of participants’ viruses tested had at least one sequence with 10-1074 resistance-associated mutations. Mutations interfering with the glycan binding site at HIV Env position 332 accounted for 95% of all observed mutations. Subsequent analysis of a larger historic dataset of 2425 B-clade envelope sequences sampled from 1983 to 2019 revealed an increase of these mutations within the population over time. Clinical studies have shown that the presence of pre-existing bNAb mutations may predict diminished therapeutic effectiveness of 10-1074. Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies.
Published: 2024
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5. Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents

Author: Oliver L. Sampson, Cecilia Jay, Emily Adland, Anna Csala, Nicholas Lim, Stella M. Ebbrecht, Lorna C. Gilligan, Angela E. Taylor, Sherley Sherafin George, Stephanie Longet, Lucy C. Jones, Ellie Barnes, John Frater, Paul Klenerman, Susie Dunachie, Miles Carrol, James Hawley, Wiebke Arlt, Andreas Groll, and Philip Goulder
Subjects: type I interferon, plasmacytoid dendritic cell, immune sex difference, androgen, adolescent vaccination, Immunologic diseases. Allergy, RC581-607
Abstract: mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.
Published: 2024
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6. Chemical Treatments on Invasive Bivalve, Corbicula fluminea

Author: Katie D. Goulder and Wai Hing Wong
Subjects: Asian clam, chemical treatment, invasive species, Corbicula fluminea, bivalve mollusc, molluscicide, Veterinary medicine, SF600-1100, Zoology, QL1-991
Abstract: The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, and South America. Due to their natural characteristics as a hermaphroditic species with a high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States, as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments for reactively controlling invasive mollusc populations and proactively preventing their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in natural open-water systems was performed to evaluate molluscicides and identify the toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize the negative impact on water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners in invasive Asian clam management.
Published: 2024
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7. Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents

Author: Cecilia Jay, Emily Adland, Anna Csala, Nicholas Lim, Stephanie Longet, Ane Ogbe, Jeremy Ratcliff, Oliver Sampson, Craig P. Thompson, Lance Turtle, Eleanor Barnes, Susanna Dunachie, Paul Klenerman, Miles Carroll, and Philip Goulder
Subjects: SARS-CoV-2, vaccine, COVID-19, adolescents, immunity, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p
Published: 2023
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8. Large-scale inference of correlation among mixed-type biological traits with phylogenetic multivariate probit models

Author: Zhang, Zhenyu, Nishimura, Akihiko, Bastide, Paul, Ji, Xiang, Payne, Rebecca P., Goulder, Philip, Lemey, Philippe, and Suchard, Marc A.
Subjects: Statistics - Methodology, Quantitative Biology - Populations and Evolution, Statistics - Computation
Abstract: Inferring concerted changes among biological traits along an evolutionary history remains an important yet challenging problem. Besides adjusting for spurious correlation induced from the shared history, the task also requires sufficient flexibility and computational efficiency to incorporate multiple continuous and discrete traits as data size increases. To accomplish this, we jointly model mixed-type traits by assuming latent parameters for binary outcome dimensions at the tips of an unknown tree informed by molecular sequences. This gives rise to a phylogenetic multivariate probit model. With large sample sizes, posterior computation under this model is problematic, as it requires repeated sampling from a high-dimensional truncated normal distribution. Current best practices employ multiple-try rejection sampling that suffers from slow-mixing and a computational cost that scales quadratically in sample size. We develop a new inference approach that exploits 1) the bouncy particle sampler (BPS) based on piecewise deterministic Markov processes to simultaneously sample all truncated normal dimensions, and 2) novel dynamic programming that reduces the cost of likelihood and gradient evaluations for BPS to linear in sample size. In an application with 535 HIV viruses and 24 traits that necessitates sampling from a 12,840-dimensional truncated normal, our method makes it possible to estimate the across-trait correlation and detect factors that affect the pathogen's capacity to cause disease. This inference framework is also applicable to a broader class of covariance structures beyond comparative biology., Comment: 24 pages, 6 figures, 2 tables. Version accepted by Annals of Applied Statistics
Published: 2019

9. Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members

Author: Cecilia Jay, Emily Adland, Anna Csala, Christina Dold, Matthew Edmans, Carl-Philipp Hackstein, Anni Jamsen, Nicholas Lim, Stephanie Longet, Ane Ogbe, Oliver Sampson, Donal Skelly, Owen B. Spiller, Lizzie Stafford, Craig P. Thompson, Lance Turtle, Ellie Barnes, Susanna Dunachie, Miles Carroll, Paul Klenerman, Chris Conlon, Philip Goulder, and Lucy C. Jones
Subjects: SARS-CoV-2, COVID-19, exposed seronegative, family, T-cells, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionFamily studies of antiviral immunity provide an opportunity to assess virus-specific immunity in infected and highly exposed individuals, as well as to examine the dynamics of viral infection within families. Transmission of SARS-CoV-2 between family members represented a major route for viral spread during the early stages of the pandemic, due to the nature of SARS-CoV-2 transmission through close contacts.MethodsHere, humoral and cellular immunity is explored in 264 SARS-CoV-2 infected, exposed or unexposed individuals from 81 families in the United Kingdom sampled in the winter of 2020 before widespread vaccination and infection.ResultsWe describe robust cellular and humoral immunity into COVID-19 convalescence, albeit with marked heterogeneity between families and between individuals. T-cell response magnitude is associated with male sex and older age by multiple linear regression. SARS-CoV-2-specific T-cell responses in seronegative individuals are widespread, particularly in adults and in individuals exposed to SARS-CoV-2 through an infected family member. The magnitude of this response is associated with the number of seropositive family members, with a greater number of seropositive individuals within a family leading to stronger T-cell immunity in seronegative individuals.DiscussionThese results support a model whereby exposure to SARS-CoV-2 promotes T-cell immunity in the absence of an antibody response. The source of these seronegative T-cell responses to SARS-CoV-2 has been suggested as cross-reactive immunity to endemic coronaviruses that is expanded upon SARS-CoV-2 exposure. However, in this study, no association between HCoV-specific immunity and seronegative T-cell immunity to SARS-CoV-2 is identified, suggesting that de novo T-cell immunity may be generated in seronegative SARS-CoV-2 exposed individuals.
Published: 2023
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10. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting

Author: Julg, Boris, Dee, Lynda, Ananworanich, Jintanat, Barouch, Dan H, Bar, Katharine, Caskey, Marina, Colby, Donn J, Dawson, Liza, Dong, Krista L, Dubé, Karine, Eron, Joseph, Frater, John, Gandhi, Rajesh T, Geleziunas, Romas, Goulder, Philip, Hanna, George J, Jefferys, Richard, Johnston, Rowena, Kuritzkes, Daniel, Li, Jonathan Z, Likhitwonnawut, Udom, van Lunzen, Jan, Martinez-Picado, Javier, Miller, Veronica, Montaner, Luis J, Nixon, Douglas F, Palm, David, Pantaleo, Giuseppe, Peay, Holly, Persaud, Deborah, Salzwedel, Jessica, Salzwedel, Karl, Schacker, Timothy, Sheikh, Virginia, Søgaard, Ole S, Spudich, Serena, Stephenson, Kathryn, Sugarman, Jeremy, Taylor, Jeff, Tebas, Pablo, Tiemessen, Caroline T, Tressler, Randall, Weiss, Carol D, Zheng, Lu, Robb, Merlin L, Michael, Nelson L, Mellors, John W, Deeks, Steven G, and Walker, Bruce D
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, Clinical Trials and Supportive Activities, HIV/AIDS, Clinical Research, 6.1 Pharmaceuticals, 6.9 Resources and infrastructure (treatment evaluation), Infection, Anti-Retroviral Agents, HIV Infections, Humans, Sustained Virologic Response, Viral Load, Withholding Treatment, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract: Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.
Published: 2019

11. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author: Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O’Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan de Silva, David Eyre, Sheila Lumley, Amy Flaxman, James Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, Chris P. Conlon, Katie Jeffery, Simon Travis, Philip Goulder, John Frater, Alex J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes, Christina Dold, and Susanna J. Dunachie
Subjects: Science
Abstract: The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.
Published: 2022
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12. Prevention of low-temperature gelation in milk protein concentrates by calcium-binding salts

Author: D.M. Goulder and F.M. Harte
Subjects: low-temperature gel, calcium-binding salt, emulsifying salt, milk protein concentrate, Dairy processing. Dairy products, SF250.5-275, Dairying, SF221-250
Abstract: ABSTRACT: The objective of this study was to determine the effect of adding low concentrations of calcium-binding salts on the prevention of low-temperature gelation in milk protein concentrates (MPC). The MPC were created by a combination of ultrafiltration and diafiltration, standardized from 14 to 17% (wt/vol) protein content and mixed with one of 5 calcium-binding salts (sodium citrate, sodium hexametaphosphate, sodium polyphosphate, sodium pyrophosphate, and sodium monophosphate) adjusted to a pH of 6.75. The flow properties, apparent viscosity, and gel strength were determined for MPC containing a wide range of calcium-binding salt concentrations. Low-temperature gelation occurred in MPC with 16.0% and higher protein content. Low-temperature gelation at 16.0% protein content was prevented by the addition of any of the 5 salts tested at low concentrations (0.30 mM or less; sodium citrate, sodium hexametaphosphate, sodium polyphosphate, sodium pyrophosphate or sodium monophosphate), with sodium polyphosphate and sodium monophosphate being the most consistent in preventing low-temperature gels. All MPC samples exhibited shear-thinning behavior (n = 0.52–0.72), which increased (lower n values) as the protein content increased and decreased by addition of salt. At concentrations of salt above 1.00 mM, thermally irreversible gels were observed with relative strength dependent on the salt and protein content.
Published: 2022
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13. Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound

Author: P. Zacharopoulou, E. Marchi, A. Ogbe, N. Robinson, H. Brown, M. Jones, L. Parolini, M. Pace, N. Grayson, P. Kaleebu, H. Rees, S. Fidler, P. Goulder, P. Klenerman, and J. Frater
Subjects: Medicine, Science
Abstract: Abstract Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning ‘post-treatment control’ remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p
Published: 2022
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14. Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

Author: Vinicius Vieira, Nicholas Lim, Alveera Singh, Ellen Leitman, Reena Dsouza, Emily Adland, Maximilian Muenchhoff, Julia Roider, Miguel Marin Lopez, Julieta Carabelli, Jennifer Giandhari, Andreas Groll, Pieter Jooste, Julia G. Prado, Christina Thobakgale, Krista Dong, Photini Kiepiela, Andrew J. Prendergast, Gareth Tudor-Williams, John Frater, Bruce D. Walker, Thumbi Ndung’u, Veron Ramsuran, Alasdair Leslie, Henrik N. Kløverpris, and Philip Goulder
Subjects: AIDS/HIV, Immunology, Medicine
Abstract: HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.
Published: 2023
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15. Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion

Author: Cecilia Jay, Jeremy Ratcliff, Lance Turtle, Philip Goulder, and Paul Klenerman
Subjects: SARS-CoV-2, seronegative, T-cells, exposed, hepatitis C, Immunologic diseases. Allergy, RC581-607
Abstract: The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen – single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted.
Published: 2023
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16. HIV control: Is getting there the same as staying there?

Author: Goulder, Philip and Deeks, Steven G
Subjects: CD8-Positive T-Lymphocytes, Animals, Macaca mulatta, Humans, HIV-1, Viremia, HIV Infections, Acquired Immunodeficiency Syndrome, Antibodies, Viral, Female, Male, Simian immunodeficiency virus, Antibodies, Neutralizing, Simian Acquired Immunodeficiency Syndrome, Viral Load, Simian Immunodeficiency Virus, Microbiology, Immunology, Medical Microbiology, Virology
Abstract: In this brief review and perspective, we address the question of whether the immune responses that bring about immune control of acute HIV infection are the same as, or distinct from, those that maintain long-term viral suppression once control of viremia has been achieved. To this end, we describe the natural history of elite and post-treatment control, noting the lack of data regarding what happens acutely. We review the evidence suggesting that the two clinical phenotypes may differ in terms of the mechanisms required to achieve and maintain control, as well as the level of inflammation that persists once a steady state is achieved. We then describe the evidence from longitudinal studies of controllers who fail and studies of biologic sex (male versus female), age (children versus adults), and simian immunodeficiency virus (SIV) (pathogenic/experimental versus nonpathogenic/natural infection). Collectively, these studies demonstrate that the battle between the inflammatory and anti-inflammatory pathways during acute infection has long-term consequences, both for the degree to which control is maintained and the health of the individual. Potent and stringent control of HIV may be required acutely, but once control is established, the chronic inflammatory response can be detrimental. Interventional approaches designed to bring about HIV cure and/or remission should be nuanced accordingly.
Published: 2018

17. Differential Immunodominance Hierarchy of CD8+ T-Cell Responses in HLA-B27:05- and -B27:02-Mediated Control of HIV-1 Infection

Author: Adland, Emily, Hill, Matilda, Lavandier, Nora, Csala, Anna, Edwards, Anne, Chen, Fabian, Radkowski, Marek, Kowalska, Justyna D, Paraskevis, Dimitrios, Hatzakis, Angelos, Valenzuela-Ponce, Humberto, Pfafferott, Katja, Williams, Ian, Pellegrino, Pierre, Borrow, Persephone, Mori, Masahiko, Rockstroh, Jürgen, Prado, Julia G, Mothe, Beatriz, Dalmau, Judith, Martinez-Picado, Javier, Tudor-Williams, Gareth, Frater, John, Stryhn, Anette, Buus, Soren, Teran, Gustavo Reyes, Mallal, Simon, John, Mina, Buchbinder, Susan, Kirk, Gregory, Martin, Jeffrey, Michael, Nelson, Fellay, Jacques, Deeks, Steve, Walker, Bruce, Avila-Rios, Santiago, Cole, David, Brander, Christian, Carrington, Mary, and Goulder, Philip
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, Infectious Diseases, HIV/AIDS, Clinical Research, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, CD8-Positive T-Lymphocytes, Genes, MHC Class I, HIV Infections, HIV-1, HLA-B27 Antigen, Humans, Immunodominant Epitopes, Viral Load, gag Gene Products, Human Immunodeficiency Virus, nef Gene Products, Human Immunodeficiency Virus, CD8(+) T cell, HIV Gag, HIV Nef, HLA, HLA-B*27, human immunodeficiency virus, CD8+ T cell, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract: The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.IMPORTANCE CD8+ T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8+ T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8+ T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.
Published: 2018

18. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells

Author: Ramsuran, Veron, Naranbhai, Vivek, Horowitz, Amir, Qi, Ying, Martin, Maureen P, Yuki, Yuko, Gao, Xiaojiang, Walker-Sperling, Victoria, Del Prete, Gregory Q, Schneider, Douglas K, Lifson, Jeffrey D, Fellay, Jacques, Deeks, Steven G, Martin, Jeffrey N, Goedert, James J, Wolinsky, Steven M, Michael, Nelson L, Kirk, Gregory D, Buchbinder, Susan, Haas, David, Ndung’u, Thumbi, Goulder, Philip, Parham, Peter, Walker, Bruce D, Carlson, Jonathan M, and Carrington, Mary
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Sexually Transmitted Infections, HIV/AIDS, Women's Health, Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Alleles, CD4 Lymphocyte Count, Cohort Studies, HIV, HIV Infections, HLA Antigens, Humans, Killer Cells, Natural, Ligands, NK Cell Lectin-Like Receptor Subfamily C, Protein Sorting Signals, Viremia, General Science & Technology
Abstract: The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.
Published: 2018

19. Resistance of Major Histocompatibility Complex Class B (MHC-B) to Nef-Mediated Downregulation Relative to that of MHC-A Is Conserved among Primate Lentiviruses and Influences Antiviral T Cell Responses in HIV-1-Infected Individuals

Author: Mwimanzi, Francis, Toyoda, Mako, Mahiti, Macdonald, Mann, Jaclyn K, Martin, Jeffrey N, Bangsberg, David, Brockman, Mark A, Goulder, Philip, Kirchhoff, Frank, Brumme, Zabrina L, Ndung'u, Thumbi, and Ueno, Takamasa
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Immunization, HIV/AIDS, Infectious Diseases, Genetics, Vaccine Related, Sexually Transmitted Infections, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Alleles, Codon, Down-Regulation, HIV Infections, HIV-1, HLA-A Antigens, HLA-B Antigens, Humans, Immune Evasion, Immunity, Cellular, Lentiviruses, Primate, Mutagenesis, Site-Directed, Phenotype, T-Lymphocytes, nef Gene Products, Human Immunodeficiency Virus, HLA, Nef, human immunodeficiency virus, immune evasion, lentiviruses, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract: Patient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate major histocompatibility complex class A (MHC-A) and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A, on average, 11 to 32% more efficiently than MHC-B. Nef genotype/phenotype analyses in a cohort of HIV-1 subtype C-infected patients (n = 168), together with site-directed mutagenesis, revealed Nef position 9 as a subtype-specific determinant of differential HLA-A versus HLA-B downregulation activity. Nef clones harboring nonconsensus variants at codon 9 downregulated HLA-B (though not HLA-A) significantly better than those harboring the consensus sequence at this site, resulting in reduced recognition of infected target cells by HIV-1-specific CD8+ effector cells in vitro Among persons expressing protective HLA class I alleles, carriage of Nef codon 9 variants was also associated with reduced ex vivo HIV-specific T cell responses. Our results demonstrate that Nef's inferior ability to downregulate MHC-B compared to that of MHC-A is conserved across primate lentiviruses and suggest that this property influences antiviral cellular immune responses.IMPORTANCE Primate lentiviruses encode the Nef protein that plays an essential role in establishing persistent infection in their respective host species. Nef interacts with the cytoplasmic region of MHC-A and MHC-B molecules and downregulates them from the infected cell surface to escape recognition by host cellular immunity. Using a panel of Nef alleles isolated from diverse primate lentiviruses including pandemic HIV-1 group M subtypes, we demonstrate that Nef proteins across all lentiviral lineages downregulate MHC-A approximately 20% more effectively than MHC-B. We further identify a naturally polymorphic site at Nef position 9 that contributes to the MHC-B downregulation function in HIV-1 subtype C and show that carriage of Nef variants with enhanced MHC-B downregulation ability is associated with reduced breadth and magnitude of MHC-B-restricted cellular immune responses in HIV-infected individuals. Our study underscores an evolutionarily conserved interaction between lentiviruses and primate immune systems that may contribute to pathogenesis.
Published: 2018

20. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author: Tomic, Adriana, Skelly, Donal T., Ogbe, Ane, O’Connor, Daniel, Pace, Matthew, Adland, Emily, Alexander, Frances, Ali, Mohammad, Allott, Kirk, Azim Ansari, M., Belij-Rammerstorfer, Sandra, Bibi, Sagida, Blackwell, Luke, Brown, Anthony, Brown, Helen, Cavell, Breeze, Clutterbuck, Elizabeth A., de Silva, Thushan, Eyre, David, Lumley, Sheila, Flaxman, Amy, Grist, James, Hackstein, Carl-Philipp, Halkerston, Rachel, Harding, Adam C., Hill, Jennifer, James, Tim, Jay, Cecilia, Johnson, Síle A., Kronsteiner, Barbara, Lie, Yolanda, Linder, Aline, Longet, Stephanie, Marinou, Spyridoula, Matthews, Philippa C., Mellors, Jack, Petropoulos, Christos, Rongkard, Patpong, Sedik, Cynthia, Silva-Reyes, Laura, Smith, Holly, Stockdale, Lisa, Taylor, Stephen, Thomas, Stephen, Tipoe, Timothy, Turtle, Lance, Vieira, Vinicius Adriano, Wrin, Terri, Pollard, Andrew J., Lambe, Teresa, Conlon, Chris P., Jeffery, Katie, Travis, Simon, Goulder, Philip, Frater, John, Mentzer, Alex J., Stafford, Lizzie, Carroll, Miles W., James, William S., Klenerman, Paul, Barnes, Eleanor, Dold, Christina, and Dunachie, Susanna J.
Published: 2022
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21. Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound

Author: Zacharopoulou, P., Marchi, E., Ogbe, A., Robinson, N., Brown, H., Jones, M., Parolini, L., Pace, M., Grayson, N., Kaleebu, P., Rees, H., Fidler, S., Goulder, P., Klenerman, P., and Frater, J.
Published: 2022
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22. HIV specific CD8+ TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control

Author: Rabiah Fardoos, Sarah K. Nyquist, Osaretin E. Asowata, Samuel W. Kazer, Alveera Singh, Abigail Ngoepe, Jennifer Giandhari, Ntombifuthi Mthabela, Dirhona Ramjit, Samita Singh, Farina Karim, Søren Buus, Frank Anderson, J. Zachary Porterfield, Andile L. Sibiya, Rishan Bipath, Kumeshan Moodley, Warren Kuhn, Bonnie Berger, Son Nguyen, Tulio de Oliveira, Thumbi Ndung’u, Philip Goulder, Alex K. Shalek, Alasdair Leslie, and Henrik N. Kløverpris
Subjects: CD8+ TRM cells, HIV, PD-1, tonsils, exhaustion, natural HIV control, Immunologic diseases. Allergy, RC581-607
Abstract: Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally TRM-like profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.
Published: 2022
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23. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

Author: Adrienn Angyal, PhD, Stephanie Longet, PhD, Shona C Moore, PhD, Rebecca P Payne, DPhil, Adam Harding, MSc, Tom Tipton, PhD, Patpong Rongkard, MSc, Mohammad Ali, MD, Luisa M Hering, MSc, Naomi Meardon, MBChB, James Austin, PhD, Rebecca Brown, PhD, Donal Skelly, PhD, Natalie Gillson, BSc, Sue L Dobson, MSc, Andrew Cross, PhD, Gurjinder Sandhar, MSc, Jonathan A Kilby, MSc, Jessica K Tyerman, BSc, Alexander R Nicols, MSc, Jarmila S Spegarova, PhD, Hema Mehta, DPhil, Hailey Hornsby, MSc, Rachel Whitham, MSc, Christopher P Conlon, ProfPhD, Katie Jeffery, PhD, Philip Goulder, ProfDPhil, John Frater, ProfPhD, Christina Dold, PhD, Matthew Pace, PhD, Ane Ogbe, PhD, Helen Brown, BSc, M Azim Ansari, DPhil, Emily Adland, PhD, Anthony Brown, BSc, Meera Chand, FRCPath, Adrian Shields, PhD, Philippa C Matthews, PhD, Susan Hopkins, PhD, Victoria Hall, PhD, William James, ProfDPhil, Sarah L Rowland-Jones, ProfDM, Paul Klenerman, ProfPhD, Susanna Dunachie, ProfPhD, Alex Richter, ProfPhD, Christopher J A Duncan, DPhil, Eleanor Barnes, ProfPhD, Miles Carroll, ProfPhD, Lance Turtle, PhD, Thushan I de Silva, PhD, Adam Harding, Adam Watson, Adrian Shields, Adrienn Angyal, Ahmed Alhussni, Alex Richter, Alexander Nicols, Alexandra Deeks, Alice Webb-Bridges, Andrew Cross, Ane Ogbe, Anni Jämsén, Anthony Brown, Anu Chawla, Christina Dold, Christopher Duncan, Christopher Conlon, Donal Skelly, Denise O'Donnell, Eleanor Barnes, Emily Adland, Esme Weeks, Gurjinder Sandhar, Hailey Hornsby, Helen Brown, Hema Mehta, Hibatullah Abuelgasim, Huiyuan Xiao, James Austin, Jarmila Spegarova, Jennifer Holmes, Jenny Haworth, Jessica Tyerman, John Frater, Jonathan Kilby, Joseph Cutteridge, Katie Jeffery, Katy Lillie, Lance Turtle, Leigh Romaniuk, Lucy Denly, Luisa Hering, M. Azim Ansari, Matthew Pace, Meera Chand, Miles Carroll, Mohammad Ali, Mwila Kasanyinga, Naomi Meardon, Natalie Gillson, Patpong Rongkard, Paul Klenerman, Philip Goulder, Philippa Matthews, Rachel Whitham, Rebecca Brown, Rebecca Payne, Robert Wilson, Sarah Rowland-Jones, Sarah Thomas, Shona Moore, Siobhan Gardiner, Stephanie Longet, Stephanie Tucker, Sue Dobson, Susan Hopkins, Susanna Dunachie, Syed Adlou, Thushan de Silva, Tom Tipton, Victoria Hall, William James, Allan Lawrie, Nikki Smith, Helena Turton, Amira Zawia, Martin Bayley, Alex Fairman, Kate Harrington, Rosemary Kirk, Louise Marsh, Lisa Watson, Steven Wood, Benjamin Diffey, Chris Jones, Lauren Lett, Gareth Platt, Krishanthi Subramaniam, Daniel Wootton, Brendan Payne, Sophie Hambleton, Sinead Kelly, Judith Marston, Sonia Poolan, Dianne Turner, Muzlifah Haniffa, Emily Stephenson, Sandra Adele, Hossain Delowar Akhter, Senthil Chinnakannan, Catherine de Lara, Timothy Donnison, Carl-Philipp Hackstein, Lian Lee, Nicholas Lim, Tom Malone, Eloise Phillips, Narayan Ramamurthy, Nichola Robinson, Oliver Sampson, David Eyre, Beatrice Simmons, Lizzie Stafford, Alexander Mentzer, Ali Amini, Carolina Arancibia-Cárcamo, Nicholas Provine, Simon Travis, Stavros Dimitriadis, Sile Johnson, Sarah Foulkes, Jameel Khawam, Edgar Wellington, Javier Gilbert-Jaramillo, Michael Knight, Maeva Dupont, Emily Horner, James Thaventhiran, and Jeremy Chalk
Subjects: Medicine (General), R5-920, Microbiology, QR1-502
Abstract: Summary: Background: Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. Methods: We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3–4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection. Findings: Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232–285). At 28 days (IQR 27–33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150–461] vs 55 [IQR 24–132] spot-forming units [SFUs] per 106 PBMCs; p
Published: 2022
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24. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

Author: Donal T. Skelly, Adam C. Harding, Javier Gilbert-Jaramillo, Michael L. Knight, Stephanie Longet, Anthony Brown, Sandra Adele, Emily Adland, Helen Brown, Medawar Laboratory Team, Tom Tipton, Lizzie Stafford, Alexander J. Mentzer, Síle A. Johnson, Ali Amini, OPTIC (Oxford Protective T cell Immunology for COVID-19) Clinical Group, Tiong Kit Tan, Lisa Schimanski, Kuan-Ying A. Huang, Pramila Rijal, PITCH (Protective Immunity T cells in Health Care Worker) Study Group, C-MORE/PHOSP-C Group, John Frater, Philip Goulder, Christopher P. Conlon, Katie Jeffery, Christina Dold, Andrew J. Pollard, Alex Sigal, Tulio de Oliveira, Alain R. Townsend, Paul Klenerman, Susanna J. Dunachie, Eleanor Barnes, Miles W. Carroll, and William S. James
Subjects: Science
Abstract: Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.
Published: 2021
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25. HLA-B*14:02-Restricted Env-Specific CD8+ T-Cell Activity Has Highly Potent Antiviral Efficacy Associated with Immune Control of HIV Infection

Author: Leitman, Ellen M, Willberg, Christian B, Tsai, Ming-Han, Chen, Huabiao, Buus, Søren, Chen, Fabian, Riddell, Lynn, Haas, David, Fellay, Jacques, Goedert, James J, Piechocka-Trocha, Alicja, Walker, Bruce D, Martin, Jeffrey, Deeks, Steven, Wolinsky, Steven M, Martinson, Jeremy, Martin, Maureen, Qi, Ying, Sáez-Cirión, Asier, Yang, Otto O, Matthews, Philippa C, Carrington, Mary, and Goulder, Philip JR
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Immunization, Vaccine Related, HIV/AIDS, Sexually Transmitted Infections, Clinical Research, Prevention, Vaccine Related (AIDS), 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, Good Health and Well Being, Adult, CD8-Positive T-Lymphocytes, HIV Envelope Protein gp160, HIV Infections, HIV-1, HLA-B14 Antigen, Humans, Immunity, Cellular, Peptides, gag Gene Products, Human Immunodeficiency Virus, CD8(+) T cells, HIV, HLA-B*14, immune control, CD8+ T cells, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract: Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.IMPORTANCE In HIV infection, although cytotoxic T lymphocytes (CTL) play a potentially critical role in eradication of viral reservoirs, the features that constitute an effective response remain poorly defined. We focus on HLA-B*14, unique among HLAs associated with control of HIV in that the dominant CTL response is Env specific, not Gag specific. We demonstrate that Env-specific HLA-B*14-restricted activity is substantially more efficacious than the subdominant HLA-B*14-restricted Gag response. Env immunodominance over Gag and strong Env-mediated selection pressure on HIV are observed only in subjects expressing HLA-B*14:02, and not HLA-B*14:01. This reflects the increased functional avidity of the Env response over Gag, substantially more marked for HLA-B*14:02. Finally, we show that HLA-B*14:02 is significantly more strongly associated with viremic control than HLA-B*14:01. These findings indicate that, although Gag-specific CTL may usually have greater anti-HIV efficacy than Env responses, factors independent of protein specificity, including functional avidity, may carry greater weight in mediating effective control of HIV.
Published: 2017

26. Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection

Author: Gatanaga, Hiroyuki, Brumme, Zabrina L, Adland, Emily, Reyes-Terán, Gustavo, Avila-Rios, Santiago, Mejía-Villatoro, Carlos R, Hayashida, Tsunefusa, Chikata, Takayuki, Van Tran, Giang, Van Nguyen, Kinh, Meza, Rita I, Palou, Elsa Y, Valenzuela-Ponce, Humberto, Pascale, Juan M, Porras-Cortés, Guillermo, Manzanero, Marvin, Lee, Guinevere Q, Martin, Jeffrey N, Carrington, Mary N, John, Mina, Mallal, Simon, Poon, Art FY, Goulder, Philip, Takiguchi, Masafumi, and Oka, Shinichi
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Prevention, HIV/AIDS, Sexually Transmitted Infections, Genetics, Infectious Diseases, 2.4 Surveillance and distribution, Aetiology, Infection, Anti-Retroviral Agents, Drug Resistance, Viral, Global Health, HIV Infections, HIV Reverse Transcriptase, HIV-1, HLA-B18 Antigen, Humans, Immune Evasion, Mutation, Missense, Polymorphism, Genetic, Pre-Exposure Prophylaxis, Rilpivirine, E138X, escape mutation, human leukocyte antigen-B*18, replication fitness, rilpivirine, International HIV Adaptation Collaborative, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract: ObjectiveLong-acting rilpivirine is a candidate for preexposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing human leukocyte antigen (HLA)-B18 where reverse transcriptase-E138X arises as an immune escape mutation. We investigate the global prevalence, B18-linkage and replicative cost of reverse transcriptase-E138X and its regional implications for rilpivirine PrEP.MethodsWe analyzed linked reverse transcriptase-E138X/HLA data from 7772 antiretroviral-naive patients from 16 cohorts spanning five continents and five HIV-1 subtypes, alongside unlinked global reverse transcriptase-E138X and HLA frequencies from public databases. E138X-containing HIV-1 variants were assessed for in-vitro replication as a surrogate of mutation stability following transmission.ResultsReverse transcriptase-E138X variants, where the most common were rilpivirine resistance-associated mutations E138A/G/K, were significantly enriched in HLA-B18-positive individuals globally (P = 3.5 × 10) and in all HIV-1 subtypes except A. Reverse transcriptase-E138X and B18 frequencies correlated positively in 16 cohorts with linked HIV/HLA genotypes (Spearman's R = 0.75; P = 7.6 × 10) and in unlinked HIV/HLA data from 43 countries (Spearman's R = 0.34, P = 0.02). Notably, reverse transcriptase-E138X frequencies approached (or exceeded) 10% in key epidemic regions (e.g. sub-Saharan Africa, Southeastern Europe) where B18 is more common. This, along with the observation that reverse transcriptase-E138X variants do not confer in-vitro replicative costs, supports their persistence, and ongoing accumulation in circulation over time.ConclusionsResults illustrate the potential for a natural immune-driven HIV-1 polymorphism to compromise antiretroviral-based prevention, particularly in key epidemic regions. Regional reverse transcriptase-E138X surveillance should be undertaken before use of rilpivirine PrEP.
Published: 2017

27. Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium

Author: Kuhn, Louise, Barnabas, Shaun, Cotugno, Nicola, Peay, Holly, Goulder, Philip, Cotton, Mark, Violari, Avy, Pahwa, Savita, Reddy, Kavidha, Tagarro, Alfredo, Otwombe, Kennedy, Fry, Samantha, Vaz, Paula, Lain, Maria Grazia, Nhampossa, Tacilta, Archary, Moherndran, Maiga, Almoustapha Issiaka, Puthanakit, Thanyawee, Kityo, Cissy M, Foster, Caroline, Rojo, Pablo, Klein, Nigel, Nastouli, Eleni, Tiemessen, Caroline T, de Rossi, Anita, Ndung'u, Thumbi, Persaud, Deborah, Lichterfeld, Mathias, Giaquinto, Carlo, Palma, Paolo, and Rossi, Paolo
Abstract: Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.
Published: 2024
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28. Predictable patterns of CTL escape and reversion across host populations and viral subtypes in HIV-1 evolution

Author: Palmer, Duncan S., Adland, Emily, Frater, John A., Goulder, Philip J. R., Ndung'u, Thumbi, Matthews, Philippa C., Phillips, Rodney E., Shapiro, Roger, McVean, Gil, and McLean, Angela R.
Subjects: Quantitative Biology - Populations and Evolution
Abstract: The twin processes of viral evolutionary escape and reversion in response to host immune pressure, in particular the cytotoxic T-lymphocyte (CTL) response, shape Human Immunodeficiency Virus-1 sequence evolution in infected host populations. The tempo of CTL escape and reversion is known to differ between CTL escape variants in a given host population. Here, we ask: are rates of escape and reversion comparable across infected host populations? For three cohorts taken from three continents, we estimate escape and reversion rates at 23 escape sites in optimally defined Gag epitopes. We find consistent escape rate estimates across the examined cohorts. Reversion rates are also consistent between a Canadian and South African infected host population. Certain Gag escape variants that incur a large replicative fitness cost are known to revert rapidly upon transmission. However, the relationship between escape/reversion rates and viral replicative capacity across a large number of epitopes has not been interrogated. We investigate this relationship by examining $in$ $vitro$ replicative capacities of viral sequences with minimal variation: point escape mutants induced in a lab strain. Remarkably, despite the complexities of epistatic effects exemplified by pathways to escape in famous epitopes, and the diversity of both hosts and viruses, CTL escape mutants which escape rapidly tend to be those with the highest replicative capacity when applied as a single point mutation. Similarly, mutants inducing the greatest costs to viral replicative capacity tend to revert more quickly. These data suggest that escape rates in Gag are consistent across host populations, and that in general these rates are dominated by site specific effects upon viral replicative capacity.
Published: 2015

29. T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Author: Ane Ogbe, Barbara Kronsteiner, Donal T. Skelly, Matthew Pace, Anthony Brown, Emily Adland, Kareena Adair, Hossain Delowar Akhter, Mohammad Ali, Serat-E Ali, Adrienn Angyal, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Helen Brown, Senthil Chinnakannan, Christopher Conlon, Catherine de Lara, Thushan de Silva, Christina Dold, Tao Dong, Timothy Donnison, David Eyre, Amy Flaxman, Helen Fletcher, Joshua Gardner, James T. Grist, Carl-Philipp Hackstein, Kanoot Jaruthamsophon, Katie Jeffery, Teresa Lambe, Lian Lee, Wenqin Li, Nicholas Lim, Philippa C. Matthews, Alexander J. Mentzer, Shona C. Moore, Dean J. Naisbitt, Monday Ogese, Graham Ogg, Peter Openshaw, Munir Pirmohamed, Andrew J. Pollard, Narayan Ramamurthy, Patpong Rongkard, Sarah Rowland-Jones, Oliver Sampson, Gavin Screaton, Alessandro Sette, Lizzie Stafford, Craig Thompson, Paul J. Thomson, Ryan Thwaites, Vinicius Vieira, Daniela Weiskopf, Panagiota Zacharopoulou, Oxford Immunology Network Covid-19 Response T Cell Consortium, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, Lance Turtle, Paul Klenerman, Philip Goulder, John Frater, Eleanor Barnes, and Susanna Dunachie
Subjects: Science
Abstract: Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.
Published: 2021
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30. Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV

Author: Ane Ogbe, Matthew Pace, Mustapha Bittaye, Timothy Tipoe, Sandra Adele, Jasmini Alagaratnam, Parvinder K. Aley, M. Azim Ansari, Anna Bara, Samantha Broadhead, Anthony Brown, Helen Brown, Federica Cappuccini, Paola Cinardo, Wanwisa Dejnirattisai, Katie J. Ewer, Henry Fok, Pedro M. Folegatti, Jamie Fowler, Leila Godfrey, Anna L. Goodman, Bethany Jackson, Daniel Jenkin, Mathew Jones, Stephanie Longet, Rebecca A. Makinson, Natalie G. Marchevsky, Moncy Mathew, Andrea Mazzella, Yama F. Mujadidi, Lucia Parolini, Claire Petersen, Emma Plested, Katrina M. Pollock, Thurkka Rajeswaran, Maheshi N. Ramasamy, Sarah Rhead, Hannah Robinson, Nicola Robinson, Helen Sanders, Sonia Serrano, Tom Tipton, Anele Waters, Panagiota Zacharopoulou, Eleanor Barnes, Susanna Dunachie, Philip Goulder, Paul Klenerman, Gavin R. Screaton, Alan Winston, Adrian V.S. Hill, Sarah C. Gilbert, Miles Carroll, Andrew J. Pollard, Sarah Fidler, Julie Fox, Teresa Lambe, and John Frater
Subjects: AIDS/HIV, COVID-19, Medicine
Abstract: Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4–6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.
Published: 2022
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31. Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Author: Emily Adland, Jane Millar, Nomonde Bengu, Maximilian Muenchhoff, Rowena Fillis, Kenneth Sprenger, Vuyokasi Ntlantsana, Julia Roider, Vinicius Vieira, Katya Govender, John Adamson, Nelisiwe Nxele, Christina Ochsenbauer, John Kappes, Luisa Mori, Jeroen van Lobenstein, Yeney Graza, Kogielambal Chinniah, Constant Kapongo, Roopesh Bhoola, Malini Krishna, Philippa C. Matthews, Ruth Penya Poderos, Marta Colomer Lluch, Maria C. Puertas, Julia G. Prado, Neil McKerrow, Moherndran Archary, Thumbi Ndung’u, Andreas Groll, Pieter Jooste, Javier Martinez-Picado, Marcus Altfeld, and Philip Goulder
Subjects: Science
Abstract: Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males.
Published: 2020
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32. Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point.

Author: Ndhlovu, Zaza, Kamya, Philomena, Mewalal, Nikoshia, Kløverpris, Henrik, Nkosi, Thandeka, Pretorius, Karyn, Laher, Faatima, Ogunshola, Funsho, Chopera, Denis, Ghebremichael, Musie, Ismail, Nasreen, Moodley, Amber, Malik, Amna, Leslie, Alasdair, Goulder, Philip, Buus, Søren, Chakraborty, Arup, Dong, Krista, Ndungu, Thumbi, Walker, Bruce, and Shekhar, Karthik
Subjects: Adolescent, Apoptosis, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes, Female, Flow Cytometry, HIV Infections, HIV-1, Humans, Kinetics, Lymphocyte Activation, Proto-Oncogene Proteins c-bcl-2, RNA, Viral, Time Factors, Viral Load, Viremia, Young Adult, fas Receptor
Abstract: CD8(+) T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8(+) T cell response, with limited bystander activation of non-HIV memory CD8(+) T cells. HIV-specific CD8(+) T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8(+) T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8(+) T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.
Published: 2015

33. COVIDTrach: a prospective cohort study of mechanically ventilated patients with COVID-19 undergoing tracheostomy in the UK

Author: A Thompson, S Wilkinson, N Kumar, G Wong, J Smith, F Franco, P Smith, A Wilson, S Ghosh, S Shepherd, A Kumar, R Brown, D Williams, M Griffiths, J Sen, M Roberts, A McGrath, D Kumar, A Walker, A Gupta, N Sharma, P Shah, M Kumar, H Jones, P Paul, I Gonzalez, A Shah, V Srinivasan, M Kelly, P Surda, K Valchanov, S Saha, R Bentley, C Hall, J Ng, C Pearce, R Harris, H Wilson, N Amin, J Phillips, D Park, C Jennings, L Wren, B McGrath, D Walker, J Ahmed, S Menon, N Jain, R Mistry, E Jackson, W Rutherford, E France, S Mahalingam, C Hogan, A Burns, T Exall, J Rodrigues, C Xie, M Rouhani, E Paramasivam, A WILLIAMSON, K STEELE, D Dawson, S Linton, M Cameron, S Biswas, S Hodges, J Collier, J Collins, S Bennett, T Ali, N Bhatti, S Suresh, J Williamson, G Ambler, C Cook, D Baker, J Bates, J Blair, P Mukherjee, A Howard, B Cosway, M Anwar, S Fang, S Meghji, H Griffiths, M Keil, F GREEN, K Hussain, A Schache, C Lockie, S Winter, J Westwood, A Hormis, P Ward, C Walker, G Sandhu, T Davies, A Lloyd, L Linhartova, C SPENCER, A Courtney, L Bates, T Martín, T Tatla, L Ritchie, P Gill, S Shannon, A Arora, R Pinto, H Turner, J Whittaker, E Warner, L Leach, A Menon, J Higginson, G Warner, A Balfour, F Cooper, A Li, S Berry, R Gohil, M Celinski, J McEwan, E Riley, S Webster, I Ahmad, M Idle, K Jolly, S Burrows, S Parmar, B Morris, A Arya, S Mustafa, E Tam, D Chakravarty, M De, A Daudia, B Tehan, R Temple, J Broad, P Andrews, D Pennell, C Smart, R D’Souza, P Praveen, DJ Lin, M Osborne, A Coombs, T Hunt, M Singer, C Smyth, R Saha, G Walton, P Bishop, U Sheikh, R O'Brien, R Bhandari, A Rovira, S Sanyal, E Yeung, A Tse, N Lawrence, P Stimpson, H Saeed, K Fan, M Ashcroft, T Jacob, J Hadley, K Goodwin, Z Abdi, D Nair, B Hill, D Whitmore, N Macartney, P Sykes, N Mercer, R Sykes, S Siddiq, Nick JI Hamilton, AGM Schilder, MM George, GM Jama, J Goulder, C Schilling, S Laha, MA Birchall, NS Tolley, P Nankivell, O Breik, P Pracy, J Osher, C Huppa, P Stenhouse, F Ryba, EK Bhargava, D Ranford, A Takhar, C Tornari, M Verkerk, C Al-Yaghchi, M Jaafar, N Cereceda-Monteoliva, A Holroyd, K Ghufoor, H O'Mahony, H Drewery, A Mulcahy, T Magos, I Balasundaram, M Heliotis, A Loizidou, D York, R Exley, KA Solanki, P Kirticumar, A Shirazian, Y Bhatt, R Natt, N Banga, K Dhadwal, I Ekpemi, R Roplekar-Bance, N Glibbery, K Karamali, T Munroe-Gray, P Sethukumar, R Vasanthan, H Lee-Six, B Misztal, S Millington, M Musalia, A Cardozo, M Dunbobbin, S Shahidi, M Chachlani, J Fussey, M Misurati, S Ashok, H Aboulgheit, S Khwaja, R Anmolsingh, B Al-Dulaimy, E Omakobia, T Browning, L Lignos, P Twose, J Heyman, D Kathwadia, T Hwara, O Judd, W Parker, TP Davis, T Stubington, H Koumoullis, E Willcocks, L Skelly, G Dempsey, K Liatsikos, B Borgatta, A Glossop, V Politidis, D Dhariwal, A Kara, G Tattersall, W Udall, P Kirkland, J Staufenberg, H Buglass, NW Wahid, A Amlani, P Deutsch, K Markham, O Barker, A Easthope, S Glaze, D Bondin, D Thorley, K Kapoor, S Sirajuddin, F van Damme, O Mattoo, E Kershaw, S Dewhurst, S Blakeley, C Chivers, L Lindsey, R Glore, H Cunniffe, D Moult, D Zolger, J Bakmanidis, S Kandiah, A Pericleous, R Sheikh, U Nagalotimath, E El-Tabal, S Ghaffar, M Dallison, E Leakey, O Sanders, A Gomati, L Moir, CB Groba, C Davies-Husband, N Seymour, R Lovett, J Lunn, A Armson, K Hilliard, S Ladan, P Tsirevelou, V Ratnam, A Muddaiah, J Coakes, R Borg, A Tsagkovits, O Mulla, N Stobbs, D Pratap, Z Ghani, J Rocke, S Snape, A Hassaan, S Beckett, R Siau, C Lamont, C Blore, D Zakai, R Moorthy, P Bothma, A Syndercombe, N Keates, M Junaid, T Antonio, A Vijendren, V Venkatachalam, M Lechner, D Chandrasekharan, J Whiteside, S Dennis, A Eldahshan, H Paw, M Colomo-Gonzalez, N Mani, B Ranganathan, N Amiruddin, A Sladkowski, AK Abou-Foul, S Kishwan, P Naredla, A Al-Ajami, S Okhovat, E Carey, N Vallabh, A. Alatsatianos, and R Townsley
Subjects: Medical technology, R855-855.5, Surgery, RD1-811
Abstract: Objectives COVIDTrach is a UK multicentre prospective cohort study project that aims to evaluate the outcomes of tracheostomy in patients with COVID-19 receiving mechanical ventilation and record the incidence of SARS-CoV-2 infection among healthcare workers involved in the procedure.Design Data on patient demographic, clinical history and outcomes were entered prospectively and updated over time via an online database (REDCap). Clinical variables were compared with outcomes, with logistic regression used to develop a model for mortality. Participants recorded whether any operators tested positive for SARS-CoV-2 within 2 weeks of the procedure.Setting UK National Health Service departments involved in treating patients with COVID-19 receiving mechanical ventilation.Participants The cohort comprised 1605 tracheostomy cases from 126 UK hospitals collected between 6 April and 26 August 2020.Main outcome measures Mortality following tracheostomy, successful wean from mechanical ventilation and length of time from tracheostomy to wean, discharge from hospital, complications from tracheostomy, reported SARS-CoV-2 infection among operators.Results The median time from intubation to tracheostomy was 15 days (IQR 11, 21). 285 (18%) patients died following the procedure. 1229 (93%) of the survivors had been successfully weaned from mechanical ventilation at censoring and 1049 (81%) had been discharged from hospital. Age, inspired oxygen concentration, positive end-expiratory pressure setting, fever, number of days of ventilation before tracheostomy, C reactive protein and the use of anticoagulation and inotropic support independently predicted mortality. Six reports were received of operators testing positive for SARS-CoV-2 within 2 weeks of the procedure.Conclusions Tracheostomy appears to be safe in mechanically ventilated patients with COVID-19 and to operators performing the procedure and we identified clinical parameters that are predictive of mortality.Trial registration number The study is registered with ClinicalTrials.Gov (NCT04572438).
Published: 2021
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34. A prognostic model for use before elective surgery to estimate the risk of postoperative pulmonary complications (GSU-Pulmonary Score): a development and validation study in three international cohorts

Author: Bravo, Laura, Simões, Joana FF, Cardoso, Victor R, Adisa, Adewale, Aguilera, Maria L, Arnaud, Alexis, Biccard, Bruce, Calvache, Jose, Chernbumroong, Saisakul, Elhadi, Muhammed, Ghosh, Dhruv, Gujjuri, Rohan, Harrison, Ewen, Ho, Michael WS, Kasivisvanathan, Veerappan, Kouli, Omar, Lederhuber, Hans, Li, Elizabeth, Löffler, Markus W, Isik, Arda, Marcus, Hani, Martin, Janet, McLean, Kenneth A, Minaya-Bravo, Ana, Modolo, María Marta, Nepogodiev, Dmitri, Pellino, Gianluca, Picciochi, Maria, Pockney, Peter, van Ramshorst, Gabriëlle, Riad, Aya, Sayyed, Raza, Sund, Malin, Gkoutos, Georgios, Bhangu, Aneel A, Glasbey, James C, Bravo, L, Cardoso, V, Glasbey, J, Chernbumroong, S, Nepogodiev, D, Simoes, JFF, Mclean, KA, Bhangu, AA, Gkoutos, G, Kadir, B, Omar, O, Revell, E, Bahrami-Hessari, M, Ahmed, Waheed-Ul-Rahman, Argus, Leah, Ball, Alasdair, Bhangu, Aneel, Bywater, Edward P, Blanco-Colino, Ruth, Brar, Amanpreet, Chaudhry, Daoud, Dawson, Brett E, Duran, Irani, Elhadi, Muhammed, Glasbey, James C, Gujjuri, Rohan R, Jones, Conor S, Harrison, Ewen M, Kamarajah, Sivesh K, Keatley, James M, Lawday, Samuel, Li, Elizabeth, Mann, Harvinder, Marson, Ella J, Mclean, Kenneth A, Nepogodiev, Dmitri, Norman, Lisa, Ots, Riinu, Outani, Oumaima, Picciochi, Maria, Santos, Irène, Shaw, Catherine, Taylor, Elliott H, Trout, Isobel M, Varghese, Chris, Venn, Mary L, Xu, William, Dajti, Irida, Gjata, Arben, Kacimi, Salah Eddine Oussama, Boccalatte, Luis, Modolo, Maria Marta, Cox, Daniel, Pockney, Peter, Aigner, Felix, Kronberger, Irmgard Elisabeth, Samadov, Elgun, Alderazi, Amer, Padmore, Greg, van Ramshorst, Gabrielle, Lawani, Ismaïl, Cerovac, Anis, Delibegovic, Samir, Baiocchi, Glauco, Gomes, Gustavo Mendonça Ataíde, Lima Buarque, Igor, Gohar, Muhammad, Slavchev, Mihail, Nwegbu, Chukwuemeka, Agarwal, Arnav, Brar, Amanpreet, Martin, Janet, Ng-Kamstra, Joshua, Olivos, Maricarmen, Lou, Wenhui, Ren, Dong-Lin, Calvache, Jose Andres, Perez Rivera, Carlos J-, Danic Hadzibegovic, Ana, Kopjar, Tomislav, Mihanovic, Jakov, Avilés Jiménez, Pablo Mijahil, Gouvas, Nikolaos, Klat, Jaroslav, Novysedlák, René, Amisi, Nicolas, Christensen, Peter, El-Hussuna, Alaa, Batista, Sylvia, Lincango-Naranjo, Eddy, Emile, Sameh, Arévalo Sandoval, Danilo Alfonso, Dhufera, Hailu, Hailu, Samuel, Mengesha, Mengistu G, Kauppila, Joonas H, Arnaud, Alexis P, Demetrashvili, Zaza, Albertsmeier, Markus, Lederhuber, Hans, Löffler, Markus W., Kwesi Acquah, Daniel, Ofori, Bernard, Tabiri, Stephen, Metallidis, Symeon, Tsoulfas, Georgios, Aguilera-Arevalo, Maria-Lorena, Recinos, Gustavo, Mersich, Tamás, Wettstein, Dániel, Ghosh, Dhruva, Kembuan, Gabriele, Brouki Milan, Peiman, Khosravi, Mohammad Hossein, Mozafari, Masoud, Hilmi, Ahmed, Mohan, Helen, Zmora, Oded, Gallo, Gaetano, Pata, Francesco, Pellino, Gianluca, Fujimoto, Yuki, Kuroda, Naoto, Satoi, Sohei, Abou Chaar, Mohamad K., Ayasra, Faris, Fakhradiyev, Ildar, Hamdun, Intisar Hisham Said, Jin-Young, Jang, Jamal, Mohammad, Karout, Lina, Elhadi, Muhammed, Gulla, Aiste, Rasoaherinomenjanahary, Fanjandrainy, Samison, Luc Hervé, Roslani, April Camilla, Durán Sánchez, Iran Irani, Gonzalez, Diana Samantha, Martinez, Laura, Martínez, María José, Nayen, Alejandra, Ramos-De la Medina, Antonio, Nunez, Jade, Outani, Oumaima, Nashidengo, Pueya Rashid, Shrestha, Ashish Lal, Jonker, Pascal, Kruijff, Schelto, Noltes, Milou, Steinkamp, Pieter, Varghese, Chris, Wright, Deborah, Abdur-Rahman, Lukman, Ademuyiwa, Adesoji, Adisa, Adewale, Osinaike, Babatunde, Seyi-Olajide, Justina, Williams, Omolara, Williams, Emmanuel, Pejkova, Sofija, Al Balushi, Zainab, Qureshi, Ahmad Uzair, Sayyed, Raza, Abo Mohsen, Mustafa, Abukhalaf, Sadi A., Cukier, Moises, Gomez-Fernandez, Hugo, Shu Yip, Sebastian, Vasquez Ojeda, Ximena Paola, Sacdalan, Marie Dione, Major, Piotr, Azevedo, José, Cunha, Miguel F., Zarour, Ahmad, Bonci, Eduard-Alexandru, Negoi, Ionut, Efetov, Sergey, Kochetkov, Viktor, Litvin, Andrey, Allen Ingabire, Jc, Bucyibaruta, Georges, Faustin, Ntirenganya, Habumuremyi, Sosthene, Imanishimwe, Alphonsine, Jean de Dieu, Haragirimana, Munyaneza, Emmanuel, Ncogoza, Isaie, Alameer, Ehab, Ndong, Abdourahmane, Radenkovic, Dejan, Chew, Min Hoe, Koh, Frederick, Ngu, James, Panyko, Arpád, Bele, Uros, Košir, Jurij Aleš, Daoud, Hassan, Blanco-Colino, Ruth, Minaya Bravo, Ana Maria, Jayarajah, Umesh, Wickramasinghe, Dakshitha, Adam Essa Adam, Mohammed Elmujtba, Rutegård, Martin, Sund, Malin, Adamina, Michel, Gialamas, Eleftherios, Horisberger, Karoline, Alshaar, Muhammad, Lohsiriwat, Varut, Charles, Shane, Isik, Arda, Leventoğlu, Sezai, Lekuya, Hervé Monka, Lule, Herman, Kopetskyi, Slava, Alsaadi, Hayder, Alshryda, Sattar, Alser, Osaid, Bankhead-Kendall, Brittany, Breen, Kerry, Kaafarani, Haytham, Mashbari, Hassan, Bonilla Cal, Fernando, Al-Naggar, Hamza, Maimbo, Mayaba, Mazingi, Dennis, Abbott, Tom, Adamina, Michel, Akhbari, Melika, Bhanderi, Shivam, Biccard, Bruce, Chakrabortee, Sohini, Costas-Chavarri, Ainhoa, Demetriades, Andreas K, Desai, Anant, Di Saverio, Salomone, Drake, Thomas, Edwards, John, Evans, Jonathan, Fiore, Marco, Ford, Samuel, Fotopoulou, Christina, Fowler, Alexander, Futaba, Kaori, Ganly, Ian, Grace James, Harelimana, Griffiths, Ewen, Hutchinson, Peter, Hyman, Gabriella Yael, Incorvia, Joseph, Jain, Ritu, Jenkinson, Michael, Khan, Tabassum, Knight, Stephen Richard, Kolias, Angelos, Kudsk-Iversen, Søren, Kwan, Tsun Yu, Leung, Elaine, Mayol, Julio, McKay, Siobhan, Meara, John G., Mills, Emily, Moug, Susan, Patel, Akshay, Perinotti, Roberto, Rice, Henry E., Roberts, Keith, Schache, Andrew, Shaw, Richard, Smart, Neil, Stephens, Matthew, Stewart, Grant D., Teasdale, Ella, Vidya, Raghavan, Wright, Naomi, Wuraola, Funmilola, Agastra, Ervis, Thereska, Dariel, Dajti, Irida, Lucchini, Sergio Martin, Laudani, Veronica, Boccalatte, Luis, Chwat, Carina, Pedraza Salazar, Ivana Ines, Pantoja Pachajoa, Diana Alejandra, Duro, Agustin, Calderón Arancibia, José Alfredo, Bright, Tim, Hollington, Paul, Zhou, Xuanyu, Kroon, Hidde M, Farfus, Anthony, Barker, John, Watson, Eleanor, Stevens, Sean, Latif, Haider, Dawson, Amanda Caroline, Chuan, Alwin, Muralidharan, Vijayaragavan, Wong, Enoch, Ackermann, Travis, Pacilli, Maurizio, Hodgson, Russell, Heriot, Alexander, Choong, Peter, Brown, Wendy, Lidder, Surjit, Yeung, Justin, Traeger, Luke, Regalo, Guillermo, Gourlay, Ralph, Pockney, Peter, Badiani, Sarit, Koh, Cherry, Putnis, Soni, Haider, Fayza, Rahman Mitul, Ashrarur, Komen, Niels, Dhondt, Bert, Cappeliez, Serge, Pigeolet, Manon, van Ramshorst, Gabrielle, Schoneveld, Martijn, Stijns, Jasper, Oosterlinck, Wouter, Flamey, Nicolas, Kpangon, Cyrille, Agbadebo, Mouhamed, Tobome, Sèmèvo Romaric, Lawani, Ismaïl, Cerovac, Anis, Vieira Barros, Aldo, Aguiar Júnior, Samuel, Baiocchi, Glauco, Campos, Heloisa Galvão do Amaral, Gross, Jefferson, José Fernandez Coimbra, Felipe, Kowalski, Luiz Paulo, Makdissi, Fabiana, Nakagawa, Suely, Pedreira Duprat Neto, Joao, Vartanian, Jose Guilherme, Yazbek, Guilherme, Zequi, Stenio C, Flumignan, Ronald, Slavchev, Mihail, Jaworska, Natalia, Dell, Angela, Shanthanna, Harsha, Martin, Janet, Behzadi, Abdollah, Nessim, Carolyn, Mozel, Michelle, St-germain, Pascal, Russell, Crispin, Groot, Gary, Safieddine, Najib, Wijeysundera, Duminda, Eskander, Antoine, Chadi, Sami, MacKenzie, Shawn, Heredia, Fernando, Villanueva, Julio, Waissbluth, Sofia, Macchiavello, Roberto, Escudero, Mario I, Fuentes, Tyare, Mimica, Ximena, Olivos, Maricarmen, Bolivar Saenz, Dinimo, Caicedo, Lina, Alzate, Juan Pablo, Luna, Joaquin, Pedraza Alonso, Nestor Fabian, Ortiz Silva, Camilo, Perez Rivera, Carlos J-, Rodriguez, Juliana, Silva-Igua, Liliana, Torres, Martha Luz, Trujillo, Lina María, Nieto Calvache, Albaro José, Balanta-Melo, Julián, Figueroa - Casanova, Rafael, García-Montoya, Oscar-Julián, Marulanda Toro, Carlos Andres, Mendoza Arango, Maria Clara, Diaz Martinez, Eneida, Gutiérrez Perdomo, Valentina, Calvache, Jose Andres, Montenegro, Emileth, Mihanovic, Jakov, Avilés Jiménez, Pablo Mijahil, Gouvas, Nikolaos, Novysedlák, René, Rodriguez-Abreu, Julia, Lincango-Naranjo, Eddy, Abouelnagah, Galal, Shehata, Sameh, Hossam Eldin Fouad Rida, Ahmed, Hassan, Ramy A., Saad, Mahmoud M., Reda Loaloa, Mohamed, Mostafa, Badr, Qassem, Mohamed, Fahmy, Mohamed, Abozied, Hesham, Azzam, Ahmed Y, Ghozy, Sherief, Sallam, Asser, Shehta, Ahmed, Emile, Sameh, Abdelkhalek, Mohamed, Samaka, Rehab, Morsy, Amr, Sherif, Ahmed Elshawadfy, Arévalo Sandoval, Danilo Alfonso, Abebe, Metasebia, Negussie, Abraham, Fisseha, Tigist, Shumbash, Kibruyisfaw, Hailu, Samuel, Yasin, Seid Mohammed, Akililu, Yemisirach Bizuneh, Megersa, Abebe, Tefera, Teshome, Melatework, Atnafu, Bahru, Tsegaye, Bereket, Bezabih, Yoseph Solomon, Sisay, Silamlak, Bekele, Kebebe, Jira, Moa, Mengesha, Mengistu G, Derilo, Habtamu, Degefa, Eyueal, Tadesse, Anteneh, Nidaw, Melkamu, Sarjanoja, Elise, Kauppila, Joonas H, Testelin, Sylvie, Boucher, Sophie, Jouffret, Lionel, Lakkis, Zaher, Zarzavadjian Le Bian, Alban, Harper, Luke, Danguy des Déserts, Marc, André, Benoît, Slim, Karem, Verhaeghe, Romain, Police, Andrea, Girard, Edouard, Chebaro, Alexandre, Subayi Nkembi, Armande, Arnalsteen, Laurent, Ballouhey, Quentin, Mege, Diane, Jeandel, Clement, Duchalais, Emilie, Bouche, Pierre-Alban, Manceau, Gilles, Crétolle, Célia, Hervieux, Erik, Girard, Noémie, Seguin-Givelet, Agathe, Gaujoux, Sebastien, De Simone, Belinda, Boisson, Matthieu, Bergeat, Damien, Arnaud, Alexis P, Fredon, Fabien, Nappi, Francesco, Kassir, Radwan, Scalabre, Aurélien, Migliorelli, Federico, Ezanno, Anne-Cecile, Seeliger, Barbara, Vaysse, Charlotte, Charbonneau, Helene, Misrai, Vincent, Abbo, Olivier, Angeles, Martina Aida, Brunaud, Laurent, Demetrashvili, Zaza, Modabber, Ali, Wolf, Sebastian, Kamphues, Carsten, Höhn, Philipp, Glowka, Tim R., Rokohl, Alexander Christopher, Bork, Ulrich, Fluegen, Georg, Horch, Raymund E., Schmedding, Andrea, Schnitzbauer, Andreas, Eberbach, Helge, Schlager, Daniel, Spelsberg, Fritz, Keppler, Lena, Hecker, Andreas, Wolfer, Susanne, Ronellenfitsch, Ulrich, Nitschke, Christine, Peiper, Christian, Hakami, Ibrahim, Welter, Stefan, Nikolaieva, Karine, Roth, Andreas, Lindert, Judith, Gousias, Konstantinos, Rissmann, Anke, Linz, Valerie Catherine, Rahbari, Nuh, Rassweiler-Seyfried, Marie-Claire, Gut, Anna Eleonora, Gempt, Jens, Reim, Daniel, Wagner, Arthur, Albertsmeier, Markus, Keppler, Alexander M., Stoleriu, Mircea Gabriel, Saier, Tim, Stadler, Josef, Kaiser, Julia Christina, Brunner, Stefan M., Pfister, Karin, Herzberg, Jonas, Nowak, Kai, Reinhard, Tobias, Stavrou, Gregor A., Königsrainer, Alfred, Konrads, Christian, Quante, Markus, Laban, Simon, Pusch von, Silke, Hirschburger, Markus, Doerner, Johannes, Wiegering, Armin, Tampaki, Ekaterini Christina, Gutiérrez Ruiz, Alitza, Rodas, Alejandra, Portilla, Ana Lucía, Recinos, Gustavo, Aguilera-Arevalo, Maria-Lorena, Carrera, Jacqueline, Barrios Duarte, Amalia, Lowey, Megan, Barillas, Sabrina, Vaishnav, Dhaivat, Gorantlu Chowdappa, Raghunandan, Madabhavi, Irappa, Bhat, Dhananjaya, Kumar Venkatappa, Sunil, Thakar, Sumit, Jain, Kavitha, Kumar, Aruna, Nagar, Manoj, Mishra, Tushar, Sekar, Arunkumar, Gupta, Anand, Kaman, Lileswar, Karthigeyan, Madhivanan, Tripathi, Manjul, Rammohan, Ashwin, Othiyil vayoth, Sudheer, Rajanbabu, Anupama, Subbian, Anbukkani, Gupta, Rahul, Raut, Monish, Evelyn. R, Nissi, Kannaiyan, Lavanya, Matai, Dr. Anil, Misra, Sanjeev, Bhende, Vishal, Muthu, Sathish, Ghosh, Indranil, Sharma, Abhishek, Bajaj, Ankur, Rajan, Shiv, Agarwal, Gaurav, Pawar, Pranay, Alexander, Philip, Vijayakumar, M, Hameed, BM Zeeshan, L, Badareesh, Chaudhry, Navneet Kumar, Baliarsing, Lipika, Dharap, Satish, Kulkarni, Amruta, Thyavihally, Yuvaraja, Pramesh, C S, Soni, Rajesh, Dube, Surya Kumar, Sharma, Shilpa, Singh, Harvinder, Bains, Lovenish, Ghodke, Rahul, Kumar, Ashwani, Sodhai, Vivek, Maji, Suvendu, Basu, Somprakas, Mahakalkar, Chandrashekhar, Kannan, Ravi, Mehraj, Asif, N, Ranganath, Phadnis, Ashish, Yadev, I, Kavalakat, Alfie, Mittal, Rohin, Vallam, Karthik Chandra, Akhavizadegan, Hamed, Rezghi Maleki, Esmaeil, Yousefzadeh Kandevani, Naser, Ikele, Hilary, McNestry, Catherine, Fleming, Christina, O’Brien, Stephen, Abd Elwahab, Sami, Davis, Niall, Javadpour, Mohsen, McDonnell, Brendan, O Connor, Clare, Bolger, Jarlath, Clancy, Cillian, Croghan, Stefanie M, Donlon, Noel, Cullinane, Carolyn, Creavin, Ben, Muheilan, Muheilan, Earley, Helen, Kabir, Syed Mohammad Umar, Fahadullah, Muhammad, Ryan, Éanna, Connelly, Tara, Zmora, Oded, Hashimoto, Daisuke, Alqudah, Majdi Ali, Alajalen, Amer, Omari, Rand Y., Ayasra, Faris, Qasem, Abdulrahman, Alawneh, Yazan, Ahmad, Amer, Aladawi, Omar, Alrayes, Bourhan, Haidar, Hanan, Husain, Shatha, Qassem, Faisal, Sumadi, Adnan, Al-Manaseer, Balqees Mahmoud, Alsunna, Zaid, Ra’ed, Hazim, Reyad Bani Hamad, Faten, Abuleil, Amro, Abou Chaar, Mohamad K., Jimaale, Elmi Ahmed Mohamed, Abu-Mehsen, Marah, Olaywah, Noor, Wafi, Omar, Ababneh, Hazim, Abu-Ismail, Luai, Khamees, Almu’atasim, Alkhatib, Ahmad, Bolatbekova, Raikhan, Kulimbet, Mukhtar, Nurgozhin, Talgat, Saliev, Timur, Zhussupov, Baurzhan, Almabayev, Ydyrys, Fakhradiyev, Ildar, Kaidarova, Dilyara, Tamoos, Khalil, Aqeelah, Ahmed, Khalefa mohammed, Alsnosy abdullah, Al maadany, Faraj, Alkadeeki, Ghadah, Gahwagi, Milad, Aldressi, Wafa, Amnaina, Mohamed, Alansari, Arowa hassan 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Okunlola, Abiodun, Williams, Omolara, Adisa, Adewale, Abdur-Rahman, Lukman, Kache, Stephen, Sale, Danjuma, Anyanwu, Lofty-John, Okereke, Chukwuma, Tolani, Musliu Adetola, Filipce, Venko, Todorovic, Lazar, Pejkova, Sofija, Stavridis, Sotir, Massoud, John George, Alsibai, Sareyah, Sultan, Rizwan, Altaf, Humera Naz, Bhatti, Abu Bakar Hafeez, Waqar, Shahzad Hussain, Aziz, Aliya, Kerawala, Asad Ali, Rai, Lajpat, Anwer, Mariyah, Tariq, Aiman, Ayub, Bushra, Niazi, Sami ullah, Naseem, Muhammad Yasir, Sarwar, Muhammad Zeeshan, Khokhar, Muhammad Imran, Zahid, Imdad Ahmad, Majid, Haroon Javaid, Talat, Nabila, Asif, Muhammad, Chaudhary, Muhammad Hamid, Farooq, Umer, Ahmad, Siddique, Mabood, Waleed, Bukhari, Syed Imran, Tariq, Muhammad, Yaqoob, Eesha, Javed, Saad, Usman Malik, Muhammad, Yaqoob, Hassan Nawaz, Cukier, Moises, Falcon Pacheco, Glenda Marina, Mas Melendez, Robinson, Paucar Urbina, Arazzelly Del Pilar, Rios Chiuyari, Jose, Otiniano Alvarado, Carlos Eduardo, Fuentes Rivera Lau, Lorena, 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Dimofte, Mihail-Gabriel, Porumb, Vlad, Kirov, Mikhail, Molitvin, Yegor, Litvin, Andrey, Pykhteev, Vadim, Raevskaya, Marianna, Efetov, Sergey, Butyrskii, Aleksandr, Alshahrani, Mushabab, Althumairi, Azah, Alzerwi, Nasser, Al Ameer, Ahmed, Madkhali, Tariq, Abddulrahman, Ghazwani, Salman, Ayoub, Abdu, Iskander, Othman, Ghunaim, Mohammed, Alharthi, Mohammed, Alzaidi, Turki M, Alyami, Mohammad, Al Amri, Abdulrahman, AlFakhri, Abdullah, Alhefdhi, Amal, Chowdhury, Sharfuddin, Nouh, Thamer, Alshehri, Ameen, Alzahrani, Abdulrahman, Alalawi, Dr Yousef, Awad, Selmy, Konate, Ibrahima, Ndong, Abdourahmane, Tendeng, Jacques, Teo, Nan Zun, Koh, Frederick, Košir, Jurij Aleš, Bele, Uros, Aqil, Sabra, Barrena López, Cristina, Sánchez Mozo, Ana, Rodriguez Infante, Antonio, Caja Vivancos, Patricia, Prieto, Mikel, Alberdi San Roman, Igor, Gomez Fernandez, Laura, Muñoz Vives, Josep Maria, Carreras-Castañer, Anna, Díaz-Feijoo, Berta, Sieira-Gil, Ramon, Turrado-Rodriguez, Victor, Sánchez López, Anna, Sánchez-Cabús, Santiago, Jimenez Toscano, Marta, Canals Sin, MªPilar, Laura, Saura García, Martin Sole, Oriol, Palazon Bellver, Pedro, Pérez-Bertólez, Sonia, Prat-Ortells, Jordi, Riba Martínez, Mireia, Rubio-Palau, Josep, Tarrado, Xavier, Nuñez, Jorge, Alonso Mendoza, Veronica, Bescós, Coro, Espin-Basany, Eloy, Espinosa-Bravo, Martin, Gil-Sala, Daniel, González-Suárez, Susana, Montferrer Estruch, Nuria, Porteiro Mariño, Lucia, Rodríguez-Tesouro, Ana, Rojas Portilla, Fabian, Tormos Pérez, M Pilar, Vives, Inmaculada, Garcia De Cortazar, Unai, Tudela, Kiara, Landaluce-Olavarria, Aitor, Estaire Gómez, Mercedes, Almoguera, Jorge, Ugarte-Sierra, Bakarne, Jimenez, Virginia, Bertrand, Marta, Cárdenas Puiggrós, Laura, Delisau-Puig, Olga, Garcia-Adamez, Jorge, Julià Bergkvist, David, Maldonado-Marcos, Eloy, Diego García, Lucia, Roldón Golet, Marta, Soto-Darias, Iván, Rahy-Martín, Aida Cristina, Enjuto, Diego, Ramos-Luengo, Adolfo, Delgado Fernandez, Juan, Lugo Duarte, Carolina, Marquez, Lucila, Crego Vita, Diana, Dziakova, Jana, Minaya Bravo, Ana Maria, Caño Velasco, Jorge, Mateo-Sierra, Olga, Quintana-Villamandos, Begoña, Rey Valcarcel, Cristina, Rio, Javier, Román García de León, Laura, Di Martino, Marcello, Prada, Jorge, Serrano González, Javier, Losada, Manuel, Castell Gomez, Jose Tomas, Corripio-Sanchez, Ramon, Forero-Torres, Alexander, Morales-Puebla, José Manuel, Perez-Chrzanowska, Hanna, Valderrabano Gonzalez, Santiago, Yebes, Alvaro, Zapardiel, Ignacio, Diez Alonso, Manuel, Morales Palacios, Nelson, Cabañero Sánchez, Alberto, Sánchez Fernández, Fátima, Abad Gurumeta, Alfredo, Abad-Motos, Ane, Corella, Fernando, Ripollés-Melchor, Javier, Sanz-Gonzalez, Rosa, Alcaraz Fuentes, Marta, Fernández Martín, Maria Teresa, Calvo Espino, Pablo, Carrasco Prats, Milagros, Fernández-López, Antonio-José, García Escudero, Damián, Garcia Soria, Vanesa, Martínez Alonso, Jesús Aarón, Ruiz-Marín, Miguel, Gómez Pérez, Beatriz, Moya-Angeler, Joaquin, Fernández Martínez, Daniel, Llaquet Bayo, Heura, Colás-Ruiz, Enrique, Bella Romera, Susana, Ruiz Velasquez, Enrique Jose, Núñez, Bernardo, Jimenez, Raul, Zabaleta, Jon, González-Gimeno, Maria Jose, Ortega Vázquez, Irene, Perez Ferrer, Antonio, Martín-Láez, Rubén, Moreno Suarez, Marcelo, Freiria Eiras, Miguel Angel, Ramallo-Solís, Irene, Gomez-Rosado, Juan-Carlos, Oliver Guillen, Jose Ramon, Achalandabaso Boira, Mar, Catalá Bauset, Juan Carlos, Domenech, Julio, Badenes, Rafael, Bernal-Sprekelsen, Juan Carlos, Sancho-Muriel, Jorge, De Andrés-Asenjo, Beatriz, Tejero-Pintor, Francisco J, Vallve-Bernal, Marc, Vazquez Melero, Alba, Sánchez Blasco, Laura, Escartin, Jorge, Duque Mallén, Victoria, Srishankar, Selvaratnam, Jayarajah, Umesh, Sooriyabandara, Charitha, Basnayake, Oshan, Gunawansa, Nalaka, Wickramasinghe, Dakshitha, Weeraddana, Prabuth dulanjan, Vimalakanthan, Thanusan, Gishanthan, Shanthamoorthy, Chandrasinghe, Pramodh, Gialamas, Eleftherios, Sauvain, Marc-Olivier, Ghazal, Ahmad, Al-Sabbagh, Yusra, Alhassoun, Turki, Maa Albared, Sara, Naem, Antoine, Alnahr, Hareth, Jisry, Ghassan, Hammed, Ali, Isik, Arda, Francis Xaviour, Okedi, Turinawe, Gaston, Mubezi, Isaac, Sikakulya, Franck K., Kakeeto, Andrew, Kabweru, Dr. Wilberforce M., Lekuya, Hervé Monka, Kiweewa, Ronald, Lule, Herman, Matovu, Paul, Isaac, Otolia, Mashhour, Mohamed, El Helw, Amin, Alshryda, Sattar, Mohamed, Awadelkarim, Abbas, Ferial Mohamed Ali, Mohammed, Diary, Aldlyami, Ehab, Kundra, Rakesh, Michael, Antony Louis Rex, Alsaadi, Hayder, Khalil, Kareem S., Dbeis, Rachel, Shaikh, Shafaque, Ferry, Jenny, Jamal, Aiman, Siddique, Haleema, Das, Rishi, Ponugoti, Nikhil, Kamarajah, Sivesh K, Rattanasirivilai, Pornjittra, Sultana, Asma, Mosley, Frances, Chan, Matthew, Bateman, Antony, Davies-Jones, Gareth, Georgiades, Fanourios, Stewart, Grant D., Ahmadi, Navid, Coonar, Aman, Baig, Mariam, Khatri, Chetan, Surendran, Arthika, Sonksen, Julian, Sinnerton, Robert, Brennan, Caitlin, Gemma, Greenhalgh, Michael, Emerson, Hannah, Singisetti, Kiran, Totty, Joshua, Wilson, Michael, Lo, Terence, Corbett, Harriet, Okonkwo, Ijeoma, Arbane, Gill, El-Boghdadly, Kariem, Kerawala, Cyrus, Parmar, Chetan, Abbott, Tom, Bath, Michael, Odejinmi, Funlayo, Sagar, Jayesh, Talwar, Rishi, Newman, Samuel, Hammond, John, Moir, John, Duric, Natalie, Szakmany, Tamas, Iftikhar Talib, Ahmar, Youssef, Mina, Lewis-Lloyd, Christopher, Lami, Mariam, Ayub, Khurram, Dean, Benjamin, Balasubramanya, Supriya, Lakpriya, Sathya, Rogers, Luke, Turner, Paul, Maher, Mark, Sigamoney, Kohila, Edwards, John, El Kafsi, Jihène, Hardie, John, Johnson, David, Henein, Christin, Hollyman, Marianne, Agarwal, Ketan, Powell, Simon, Chauhan, Govind Singh, Patel, Rakesh, Gagnier, Joel, Carmichael, Heather, Olson, Kristofor A., Etchill, Eric, Incorvia, Joseph, Hirji, Sameer, Naunheim, Matthew, Drake, Frederick, Kaafarani, Haytham, Reinke, Caroline, Alecci, Anna, Vaysburg, Dennis, Rodriquez, Jennifer, Shih, Emily, Ban, Vin Shen, Coleman, Julia, Rice, Henry E., Kaups, Krista, Giorgakis, Emmanouil, DiNome, Maggie, Bhutiani, Neal, Bankhead-Kendall, Brittany, Aiken, Taylor, Diehl, Thomas, Gosain, Ankush, Rattan, Rishi, Ghani, Muhammad Owais Abdul, Ruzgar, Nensi Melissa, Liveris, Anna, Glass, Nina, Paranjape, Charu, Chin, Theresa, Meola, Antonio, Nicholson, Kristina, Squiers, John, Lueckel, Stephanie, Reisenauer, Janani, Callcut, Rachael, Mansour, Ahmed, Berndtson, Allison, Kornblith, Lucy, Seegert, Sara, Martins, Paulo, Al-Naggar, Hamza, Al-Shehari, Mohammed, Al-Raimi, Ibrahim, Ngulube, Allan, Siamuchembu, Maphios, Mushiwokufa, Willard, Mlambo, Busisiwe, Chinyowa, Simbarashe, Agastra, Ervis, Bollano, Enton, Dajti, Irida, Zijaj, Lorena, Fatima zohra, Belabbes, Bali, Oussama, Benallel, Nassim, Abdoun, Meriem, Bouchenak, Kamel, Soualili, Zineddine, Bastet, Joaquin, Capitaine, Daniel, Centeno Lozada, Jorge, Esquivel, Carlos, Figueroa, Rodrigo, García, Pablo Martín, Mondino, Jose, Traverso, Rogelio, Berber, Norberto, Di Vincenzo, Marcela, Grassano, Bianca, Maricic, Maximiliano, Zezular, Damaris Idara Anabel, Abuawad, Carla, Albani Forneris, Agustin, Brandariz, Rodrigo, Burchakchi, Arturo, Buttaro, Martin, Cano Busnelli, Virginia, Carminatti, Tomas, Cereghini, Julian, Crespi Amor, María Sol, Figari, Marcelo, Gonzalez Salazar, Esteban, Higuera, Felipe, Llano, Lionel, Lobos, Pablo, Mc Loughlin, Santiago, Mendoza, Efrain, Mercado, Pedro, Moyano, Pablo, Noll, Florencia, Odetto, Diego, Ramos, María Lourdes, Saadi, Jose, Scherñuk, Jordán, Slullitel, Pablo, Taboada, María Victoria, Vagni, Roberto, Montal, Silvina, Alvarez, Fernando Andres, Bruera, Nicolás, Parodi, Matias, Picon molina, Héctor, Belisle, Diego, Esteban, Agustin, García, José Sebastian, Granero, Lucas, Yaryura Montero, José Gabriel, D’Addino, José Luis, Calderón Arancibia, José Alfredo, John, Brooke-Smith, Mark, Hii, Amanda, Kundu, Nikhil, Marshall-Webb, Matthew, McVeay, Christina, Ong, Bee Shan, Parker, Dominic, Barnett, Dylan Richard, Buddingh, Karel, Dobbins, Christopher, Dudi-Venkata, Nagendra, Haque, Izhar-Ul, Herath, Matheesha, Kroon, Hidde M, Lim, Alicia, Moller, Cea-Cea, Neo, Eu Nice, Neo, Eu Ling, Russell, Christine, Tourani, Saam, Tran, Steven, Yin, Yijie, Watson, Matthew, Barker, John, Rugendyke, Anya, Watson, Eleanor, Sercombe, Ashleigh, Tee, Chin Li, Batstone, Martin, Field, Michael, Scott, Benjamin, Stevens, Sean, Charlton, Gabriella, Chen, Si, Gauri, Neha, Hayhurst, Ross, Jang, Seyoung, Zhang, Helen, Latif, Haider, Nagra, Sonal, Rudock, Gareth, Tan, Hannah, Underwood, Kirk, Youssef, Daniel, Bengeri, Savitha, Cheah, Hock Ping, Chen, Paul, Clark, Sara, Dawson, Amanda Caroline, Devan, Eliya, Fitt, Sophia, Gaul, John, Jolly, Danielle, Kane, James Dimitri, Kwok, Kelvin, Laura, Sharon, Lee, Vivian, Liang, Ina, Luo, Haili, Miles, Stephanie, Noor, Anthony, Simpson, Renwick, Cox, Aram, Thani, Nova, Egoroff, Natasha, Farik, Shebani, Moss, Jana-Lee, Wright, Deborah, Salama, Paul, Phan, Du, Townend, David, Chuan, Alwin, Barnett, Stephen, Hasan Kheslat, Hajar, Jamieson-Grigg, Chloe, Larner, Brett, Proud, David, Riddiough, Georgina, Seevanayagam, Sivendran, Zhao, Chris, An, Vinna, Drake, Anna, Hunt, Benjamin, Jain, Anshini, Lim, Christopher Seng Hong, Luck, Tara, Maroske, Georgia, Roubos, Nicholas, Sengupta, Shomik, Tsigaras, Zac, Ward, Salena, Zhou, Jessie, Coates, Amy, Nataraja, Ramesh, Pacilli, Maurizio, Gillard, Andrew, Petrakis, Nikki, Qureshi, Maryum, Seow, Sean Ezekiel, Vivian-Taylor, Josephine, Wheatley, Jennifer, O’Connor, Brendan, Teague, Warwick, Hii, Michael Wei, Isaacs, Anna, Johnson, Mary Ann, Price, Veronique, Rowcroft, Alistair, Shaw, Kalai, Stark, Claire, Lauritz, Brianne, Ong, Chui Foong, Tang, Howard, Davis, Amelia, Peerally, Bibi Nabeeha, Aubin, Anne-Marie, Gourlay, Ralph, Lim, Zhi Ying, Alsoudani, Ali, Amico, Francesco, Anning, Rebecca, Dale, Tyson, Duggal, Anchal, Ennis, Brendan, Fu, Yi Xin Joanna, Gani, Jonathan, Gelzinnis, Scott, Hadlow, Claudia, Hardstaff, Ruth, Lau, Wayne Yan, Liang, Hsin-Ping, Lim, Daniel, Mcilwain, Elysse, Ming, Yan Joyce, Ocsan, Ryan James, Organ, Nicole, Paterson, Amanda, Perez Cerdeira, Marisol, Ting, Caleb, Willoughby, Ellisha, Bailey, Ashley, Narayanan, Viswanathan, Wilkes, Anna, Zhao, Jie, D’Souza, Carl, Forbes, Clara, Haddleton, Monique, Mohammed Abdul, Naseer, Archer, Leigh, Dilevska, Tina, Hans, Tasvinder, Kumar, Mohit, Pham, Terence, Picazo Pineda, Fernando, Suk-Udom, Supisara, Jeyamanoharan, Nivedan, Sala, Michael, Dravid, Madhulika, McCartney, Conor, Sam, Apostolou, Christos, Berney, Christophe, Lam, Andrew, Ma, Vanessa, Cope, Jennifer, Llorando, Alyssa, Mahin, Humaira Haider, Putnis, Soni, Syed, Faisal, Ireland, Patrick, Zhu, Bonnie, Zitt, Matthias, Königsrainer, Ingmar, Allmer, Caterina, Mitteregger, Martin, Seitinger, Gerald, Duller, David, Mathew, Erwin, Skias, Christoph, Brinskelle, Petra, Holzmeister, Clemens, Kahn, Judith, Kresic, Josip, Lindenmann, Joerg, Lumenta, David, Puchwein, Paul, Singer, Georg, Wolf, Axel, Arco, Daniel, Kilic, Nura, Widschwendter, Peter, Freyschlag, Christian, Graber, Michael, Hirsch, Jakob, Kuen, Marlene, Liebensteiner, Michael, Messner, Franka, Messner, Alex, Naegele, Felix, Osl, Antonia, Ower, Cornelia, Rauchegger, Teresa, Reimer, Daniel, Sokolovski, Filipp, Süss, Markus, Thaler, Martin, Zehetner, Claus, Allerstorfer, Jakob, Haslhofer, David, Pisecky, Lorenz, Poier, Nikolaus, Schmolmüller, Christoph, Zwittag, Paul, Windischbauer, Amadeus, Fischer, Ines, Kirchweger, Patrick, Saini, Thomas, Berger, Julian, Fraz, Wolfgang, Nia, Arastoo, Kenez, Mihaly, Nichita, Margit, Noe, Chiara, Borhanian, Kurosch, Emmanuel, Klaus, Gantschnigg, Antonia, Grechenig, Michael, Gruber, Ricarda, Manzenreiter, Lisa, Schredl, Philipp, Weitzendorfer, Michael, Gruber, Michaela, Grünbart, Martin, Kemmetinger, Vanessa, Mosshammer, Victoria, Schaetz, Tobias, Lanner, Maximilian, Binder, Alf-Dorian, Bernardi, Martin H., Dawoud, Christopher, Foessleitner, Philipp, Grimm, Christoph, Pesta, Maximilian, Pillerstorff, Robert, Riss, Stefan, Scheriau, Georg, Fisus, Andreea, Ruiss, Manuel, Meindl, Nikolaus, Primavesi, Florian, Steiner, Florian, Falkensammer, Eva, Knotzer, Hans, Trivik-Barrientos, Felipe, Alam, Mahmood, Haider, Fayza, Mulla, Husain, Qader, Kawthar, Shirazi, Ahmed, Juma, Isam, Waheed Akbar Mohamad Akbar Nawab Deen, Fatema, AbdulQadir, Seemal, Jabr, Abdulla, Almoosa, Noora, Alam, Mohammed Shadrul, Basher, AKM Khairul, Islam, S.M. Nazmul, Khan, Sadia, Mannan, Iftekhar Ibne, Corbin, Sasha, O’Shea, Margaret, Phillips, Emil, Straltsov, Vladislav, Lyzikov, Alexei, Borges, Mafalda, Vleminckx, Nils, Bontinck, Julie, Van Haver, Anne-Sophie, Cappeliez, Serge, Pigeolet, Manon, Viste, Claire, Van Daele, Elke, Jansen, Yanina, Messaoudi, Nouredin, Ruyssers, Michael, Schoneveld, Martijn, Van Eetvelde, Ellen, Oosterlinck, Wouter, Flamey, Nicolas, Akpla, Marcellin, Agossou, Hermann, Aouagbe Behanzin, Hulrich, Agbadebo, Mouhamed, Yome, Hugues, Boukari, Alassan, Amossou, Labissi Francois, Dossou, Francis, Boras, Miran, Čuljak Blagojević, Ivana, Gunaric, Filip, Letica, Ludvig, Martinovic, Vlatka, Miskovic, Josip, Rastović, Pejana, Sesar, Irena, Favaretto Filho, Rodolfo Jose, Rodrigues, Rodrigo, Schalge Campioto, Débora, Alonso, Nivaldo, Fernandes Rezende, Ricardo, Marson, Fernando Augusto Lima, Accorsi Neto, Alfeu, Accorsi, Guilherme, Machareth, Camila, Viegas Moura, Barbara, Guarienti, Luciano, Becker, Karin, Dias, Andre, Girardi Fachin, Camila, Stychnicki, Adriano Seikiti, Avelino, Melissa, Lima Buarque, Igor, Francisca, Elaine, Amorim, Robson, Bellotti Leão, Maria Eduarda, Melo da Camara, Isabelle, Silva Junior, Rubem Alves, Soares Da Silva Menezes, Agna, Cavazzola, Leandro Totti, Roloff Cardoso, Guilherme, Silva Neto, Brasil, Soares, Tilaê, Guerra, Enilde Eloena, Salem, Moacyr, de Campos Prado, Caio Antonio, Zani, Ana Carolina Tagliatti, Lourenço Gomes dos Santos, Carolina, Quintana, Silvana Maria, Veccechi Bijos Zaccaro, Marília, Lima, Leonardo, da Cunha Viana Júnior, Alonço, Trindade Martins, Isabela, R Oliveira, Priscila, Schmitz Nunes, Kamilla, Abdallah, Emne, Aguiar Júnior, Samuel, Baiocchi, Glauco, Campos, Heloisa Galvão do Amaral, Facure, Luciana, Kupper, Bruna, Leite, Fernanda, Marques, Narimã, Nakagawa, Suely, Scintini Herbst, Ana Carolina, Soares Dos Santos, Silvana, Vartanian, Jose Guilherme, Zequi, Stenio C, Gonçalves, Rodrigo, Machado, Vinicius, Nadal, Luis Roberto, Pansani, Adrieli, Simonsen, Marcelo, Tsuchiya, Daniela, Vasconcelos, Vladimir, Kim, Nam Jin, Nunes, Rafael, Pinto, Fabio, Sigoli Pereira, Thiago Henrique, Volpe, Gustavo Jardim, Nardi, Caroline, Braz de Oliveira, Layze, Ribeiro, Ivonizete Pires, Sousa, Álvaro Francisco Lopes de, Freitas, Marcelo Augusto Faria, Rodrigues da Cunha, Juliano, Dimitrov, Dobromir, Gohar, Muhammad, Gyokova, Elitsa, Neykov, Vasil, Atanasov, Boyko, Slavchev, Mihail, Kamenova, Paolina, Yotsov, Tsanko, Spassov, Kolyo, Tsankov, Tsanko, Brown, James, Bali, Krittika, Bigam, David, Dajani, Khaled, Dell, Angela, Hong, Dennis, Luketic, Lea, Mayer, Robert, McGee, Jacob, Yang, Homer, Behzadi, Abdollah, Brar, Amanpreet, Hanson, Melissa, Hopkins, Brent, Merchant, Richard, Mozel, Michelle, Belzile, Etienne, Boucher-Kovalik, Sofia, Corriveau-Durand, Simon, Cote, Mathieu, Côté, Mathilde, Demers, Suzanne, Desbiens, Christine, El Ouazzani, Mehdi, Gosselin, Karo, Maheux-Lacroix, Sarah, Nadeau, Sylvie, Nguyen, Sebastien, Pelet, Stéphane, Groot, Gary, Wood, Melissa, Atrey, Amit, Ellenbogen, Yosef, Kellett, Sorcha, Suresh, Hrishikesh, Eskander, Antoine, Gentili, Fred, St. Jacques, Leslie, Tabasinejad, Raha, Hsiao, Marvin, MacKenzie, Shawn, Broe, Claire, Grey, Rebecca, Lindberg, Andrew, Mata Gutierrez, Juan, Phillips, Drew, Heredia, Fernando, Fernández, Esteban, Ochoa Gaete, Katherine, Sandoval Tobar, Mauricio, Reyes, José Tomás, Rivera, Barbara, Cohn, David, Recabal, Pedro, Sandoval, Camilo, Pincheira, Camila, Torres, Janina, Valenzuela, Marco, Yang, Kun, Zhang, Yuexin, Cunchuan, Wang, Yang, Wah, Liang, Tingbo, Caicedo, Camilo, Perez Granados, Carolina, Luna, Joaquin, Serrano, Oscar, Ortiz Silva, Camilo, Vega Calvera, Andrea Juliana, Acosta Buitrago, Lina M., Cabrera Rivera, Paulo Andrés, Cormane Alfaro, Valeria, Guerrero-Becerra, Albert Franz, Kadamani Abiyomaa, Akram, Polanía Sandoval, Camilo Andrés, Roman Ortega, Carlos Fernando, Téllez, Manuela, Arias-Amézquita, Fernando, Escorcia, Elkin, Herrera-Almario, Gabriel, Monsalve, Guillermo, Caicedo Giraldo, María Alejandra, Castillo Florez, Maria Carolina, Cendales, María Angelica, Daniel, Mario, Espitia, Hernando, Navarro, Juan Carlos, Parra Abaunza, Katherine, Pulido, Eliana, Riveros Castillo, William Mauricio, Rubiano, Wilson, Salgado Tovar, Javier Mauricio, Trillos, Marcial, Villate leon, Juan pablo, Becerra Mendez, Luis, Beltran, Rafael Jose, Calderon Quiroz, Pedro Hernando, Cervera Bonilla, Sergio, Garcia Mora, Mauricio, Mariño, Ivan, Pinilla Morales, Raúl Eduardo, Puerto, Angela, Quintero-Ortíz, Ma. Andrea, Suarez, Raul, Velez Bernal, Jorge Luis, Camargo Gómez, Daniela, kammerer, Christian, Acuna Saravia, Maria Fernanda, Arroyave, Roberto, Barreto Angulo, Jose Maria, Dueñas-Ramirez, Juan Carlos, Escobar Vidarte, Oscar Andres, Gomez, Laura, Gomez, Alejandro, Herrera Castañeda, Enrique, Hinaoui, Marisol, Idrobo Escobar, Anuar Armando, Llanos Lucero, Carlos Antonio, Montoya Casella, Antonio José, Perea Serna, Andrea Carolina, Ríos-Samper, Gabriel, Sandoval, John, Sarmiento Ramirez, Guillermo Alberto, Zuluaga Zuluaga, Mauricio, Figueroa, Juan Sebastian, Gonzalez Mosos, Maria Fernanda, Jaramillo Roncancio, Juan Jose, Mosos, Monica, Ramirez, Juan Sebastian, Idarraga Ramírez, Leidy Natalia, Marin Gonzalez, Ana Maria, Mejia, David Alejandro, Vanegas, Luis Emiro, Aruachan Vesga, Sandra, Diaz Martinez, Eneida, Martinez Estrada, Gustavo Antonio, Giraldo Velasquez, Angela Maria, Tovar, Jesus Hernan, Tovar, German Alirio, Buesaquillo, Christian Ali, Olave Montaño, Victor David, Montenegro, Emileth, Genda, Eben-ezer, Eboma, Fabrice, Grulović, Karlo, Bosak Versic, Ana, Srsen Medancic, Suzana, Brkic, Lucija, Cokarić, Sara, Tomić, Josipa, Brzic, Domagoj, Dijan, Emilio, Grgec Dragicevic, Maja, Konjevoda, Suzana, Morović, Domagoj, Perišić, Gordan, Zuzul, Matea, Anzic, Srdan Ante, Carevic, Iva, Biočina, Bojan, Bobovec, Dino, Bumber, Boris, Duric Vukovic, Katarina, Jelčić, Ivan, Kastelan, Zeljko, Kolak, Juraj, Pasini, Miram, Penezić, Luka, Prstacic, Ratko, Romić, Ivan, Tomic, Mislav, Luksic, Ivica, Avilés Jiménez, Pablo Mijahil, Panayiotou, Yiannis, Stavrinidou, Olga, Yiallourou, Anneza, Michal, Burda, Lukáš, Gawel, Wladyslaw B., Lerch, Milan, Macečková, Nicole, Simetka, Ondrej, Vavra, Petr, Zelenik, Karol, Přibyl, Martin, Klíma, Karel, Pirmorad, Setareh, Hotová, Zuzana, Mladěnka, Aleš, Bozo, Nulvin, Hviid, Louise, Kristensen, Helle Ø, Paulsen, Laerke, Ebbehøj, Anders Lyng, Jönsson, Maria Lovisa, Krarup, Peter-Martin, Otte, Helena, Smith, Henry, Bælum, Jens Kristian, Ellebæk, Signe Bremholm, Batista, Sylvia, Collado Expósito, María Mabel, Crespo, Aldo, D’óleo García, Claudio Samuel, Figueroa, Jatnna, Garcia-Dubus Rodriguez, U, Guzman, Lillian, Lopez, Ariela, Maletta Francisco, Leeany, Munoz, Herisardy, Perez Fernandez, Maricely Ambar, Rodríguez, Ada, Soto, Joel, Ubinas, Raul, Villegas, Aaron, Acra-Tolari, Ricardo, Beltran, Larissa, Betances, Luis Fernand, Díaz Vásquez, Pedro Pablo, Fernandez, Damaris, Figueroa Germosen, Jiomar Manuel, Mejia De la Cruz, Dolores, Ortiz De La Cruz, Fabio, Pelletier, Gabriela, Próspero Enrique, Rodriguez Pumarol, Suero Almanzar, Irina, Lincango-Naranjo, Eddy, Negrete Ocampo, José Ricardo, Sallam, Ibrahim, Sherief, Mohamed, Abdou, Mostafa, Abo Shanab, Ahmed, Abodeeb, Aya, Aboelkhel, Roger, Abosamak, Nour Eldin, Abouelnagah, Yossof, Adel, Dina, Ahmed, Sara, Alberkamy, Abdelrahman, Ali, Ahmed, Ashraf, Olfat, Darwish, Sara, El kharashy, Rasha, Elbadawy, Seifeldin, Elsaka, Alromisaa, Ewedah, Moataz, Ezz, Yara, Gadelrab, Ziyad, Hafez, Nour, Hafez, Youssef, Hassanin, Mohamed, Hussein Aly Salama Aly, Hamza, Ibrahim, Abdelrahman, Mahmoud Abo shabana, Alaa, Mourad, Mohamed, Mubarek, Kamilia, Omar, Samaa, Ragal, Marawan, Romany, John, Salem, Alaa, Samir Abdelaal, Ahmed, Shehata, Sameh, Shehata, Abdelrahman, Shenit, Karim, Yehia, Nermin, Khaled Mohamed Eid, Omar, Ibrahim Elsayed, Omar, Shehata, Mostafa Ahmed, Abd El-Ghani, Wael, Abd Elazeem, Hossam Aldein S., Abdalla, Shimaa, Abdel-Aleem, Mahmoud, Abdelfattah, Mahmoud, Abdelhafez, Mohammed, Abdelkarem, Mohamed M., Abubeih, Hossam, Ahmed, Nagm Eldin Abu Elnga, Ahmed, Ahmed, Ahmed Saad, Sarah, Ali, Abdelrahman Ahmed Abdelrahman, Elmaghraby, Khaled, Elsdfy, Shady, Eltayeb, Almoutaz, Essam, Esraa, Gadelkareem, Rabea, Ghoneim, Ahmed, Hamada Takrouney, Mohammed, Hasan, Ahmad, Hassanin, Mohamed Abdelghafor, Mahran, Wesam, Mahrous, Doha, Ragab, Abdelrahman, Sabry, Aya, Safwat, Hadeer, Saleh, Ahmed, Samir, Ahmed, Sayed, Esraa, Taher, Mohamed Gamal, Yousof, Ebrahim Ahmed, Youssef, Ahmed, Zein Elabedeen, Omar, Ali, Samar, Elbehairy, Gehad, Eleisawy, Mahmoud, Elgendy, Abdelrahman, Elhawary, Rewan, Hamdy, Mahmoud, Hassan, Gehad, Nowar, Mostafa, Sabry, Hesham, Tarek Said-elnaby, Ahmed, Zahed, Mohamed, Zahran, Mohamed, Zoghary, Ahmed Zaki, Atef, Mohamed, Abdelhamid, Mahmoud Hossameldin Saad, El Fiky, Lobna, ElGarhy, Ibrahim, Qassem, Mohamed, Wahba, Abdelrahman, Youssif Omar Fouad, Omar, Abdelsamed, Ahmed, Elsalhy, Mohamed, Eldesouky, Omnia, Wael Mostafa Khalil Bahi, Abdullah, Tawheed, Ahmed, Al-oribi, Saeid, Aly, Nuran Khaled, ElFiky, Mahmoud, Nabil, Ahmed, Samir Farahat, Ahmed, Soliman, Mostafa, Ghaly, Galal, Abbas, Alzhraa Salah, Ibraheem, Maher, Bakry, Abdelrahman, Jammal, Mohamed, M Makram, Abdelrahman, Adel abdelaty, Ahmed, Fayad, Elsayed A., Sallam, Moataz, Shehta, Ahmed, Elfeki, Hossam, Elsaid, Mahmoud, Mostafa, Mohamed, Sakr, Ahmed, Shetiwy, Mohamed, Tawakl, Noura, Yunes, Asmaa, Atallah, Khalid, Shetiwy, Mosab, Abdelmawla, Ahmed, Abdrabou, Ahmed, Abubakr, Asmaa, Al Gohary, Rawda, Elsabagh, Alaa, Elshabrawy, Enas, Hafez, Ahmed, Mikhail, Pola, Mohamed, Mervat, Nada, Ahmed, Omran, Janna, Salem, Osama, Selim, Salma, Shalaby, Ghada, Wahbah, Mahmoud, Zakaria Abdelbary, Eman, Zayan, Ahmad Helmy, Afify, Abdelrahman, Mohamed Ahmed, Mostafa, Abdeldayem, Hesham, Abdelkader Salama, Ibrahim, Ammar, Khaled, Ayoub, Islam, Gad, Emad Hamdy, Hammad, Essam, Macshut, Mahmoud, Sherif, Ahmed Elshawadfy, Shoreem, Hany, Soliman, Hossam Eldeen, Eldaly, Abdullah, Mashaly, Sarah, Abd-Elsalam, Sherief, Abdel-Elsalam, Wafaa, Morsy, Mohamed Sherif, Nasreddin, Mohammed, Sarsik, Sameh, Kams, Liisa, Rätsep, Tõnu, Riips, Karolin, Abebe, Kirubel, Asfaw, Fitsum, Eshete, Mahder, Gedefaw, Yetsedaw, Menjeta, Abeje, Muleta, Mahteme Bekele, Sefera, Sena, Teklu, Daniel, Tirfe, Leake, Worku, Bereket, Eado, Yegeremu, Negussie, Abraham, Woldemariam, Mersha Abebe, Alemu, Megersa, Azmach, Dawit, Mamo, Dr.Mickyas, Menkir, Abel, Woldemariam, Dereje, Wubishet, Estifanos, Supha, Melka, Abebe, Nebyou, Chanie, Abera, Gebre, Hiwot, Laeke, Tsegazeab, Mammo, Tihitena Negussie, Sahlu, Abat, Tiruneh, Abraham Genetu, Zewdneh, Betelhem, Fentaw, Jibril, Tabore, Ketema, Addisalem, Abreha, Tassew, Abdissa, Desalegn, Tesfaw, Mequannet, Asmamaw, Dawit, Bedane, Dereje, Bekele, Ephrem, Getie, Aderaw, Girma, Adissu, Shimelash, Dagim, Ayalew, Tewabe, Kassahun, Berhanu, Mulugeta, Esubalew, Sisay, Silamlak, Ibrahim, Adem, Mekete, Alem, Mohammed, Adnan Abdulkadir, Abdullahi, Yasir Younis, Adem, Ephrem, Siyoum, Eneyew Getachew, Zeleke, Ewunetu, Degefe, Derje Worku, Derilo, Habtamu, Eliyas, Nebiyu, Deressa, Yadani, Melese, Lemi, Muleta, Lemesa, Teshome, Abraham, Tesso, Birhanu, Gebrekirstos, Dr.Gebreagziabher, Pitkänen, Joel, Qian, Cheng, Sinikumpu, Jaakko, Dakpé, Stéphanie, Devauchelle, Bernard, Lavagen, Nolwenn, Bastard, François, Bin, Kim, Moukoko, Didier, Alshawared, Fadi, Beyrne, Carlos Daniel, Lugans, Laurene, Doussot, Alexandre, Onorati, Ilaria, Radu, Dana, André, Benoît, Marion, Herjean, Trilling, Bertrand, Boleslawski, Emmanuel, Noiret, Barbara, Aubry, Estelle, Subayi Nkembi, Armande, Christou, Niki, Usseglio, Julie, Jeandel, Clement, Denis, Waast, Duchalais, Emilie, Regenet, Nicolas, Rigaud, Jerome, Anract, Philippe, Dohan, Anthony, Cazelles, Antoine, Chamouni, Alexandre, Karoui, Mehdi, Mejean, Arnaud, Crétolle, Célia, Thouement, Clermidi, Pauline, Hervieux, Erik, Langlais, Tristan, Leonelli, Lorenzo, Thomin, Anne, Athiel, Yoann, Cathala, Nathalie, Levy-Zauberman, Yael, Macek, Petr, Mombet, Annick, Ollat, Didier, Fabrice, Chartier-Kastler, Emmanuel, Chereau, Nathalie, Melot, Charlotte, Turco, Célia, Chouillard, Elie, Boisson, Matthieu, Frasca, Denis, Livin, Marie, Mahmoud, Fedy, Sulpice, Laurent, Arnaud, Alexis P, Cazemajou, Clément Thierry, Nyangoh Timoh, Krystel, Renault, Annaëlle, Nappi, Francesco, Ezanno, Anne-Cecile, Cherkaoui, Zineb, Vix, Michel, Gornes, Hugo, Berthoumieu, Pierre, Misrai, Vincent, Pierre, Trocard, Angeles, Martina Aida, Del, Mathilde, Vancon, Antoine, Machemedze, Solomon, Muhemi, Roger, Ndizeye, Olivier, O’Connor, Jennifer, Tchoba, Simplice, Modabber, Ali, Schäfer, Benedikt, Wallqvist, Julia, Ziemann, Sebastian, Anthuber, Matthias, Broecheler, Tobias, Goßlau, Yvonne, Maksymiw, Florian, Sommer, Florian, Sommer, Björn, Loch, Florian N, Aghalarov, Ilgar, Braumann, Chris, Höhn, Philipp, Horn, Julian, Egger, Eva, Enderes, Jana, Strieth, Sebastian, Treede, Hendrik, Wittmann, Maria, Marche, Benedikt, Schulz, Sissy-Amelie, Fuchs, Hans, Bork, Ulrich, Meisel, Cornelia, Petzold, Andrea, Fluegen, Georg, Knoefel, Wolfram Trudo, Solodarenko, Oleksandra, Grützmann, Robert, Hackner, Danilo, Faqar-Uz-Zaman, Sara Fatima, Schnitzbauer, Andreas, Fung, Christian, Leiber, Christian, Neidert, Nicolas, Sandkamp, Richard, Schlager, Daniel, Strähle, Jakob, Spelsberg, Fritz, Becker, Johannes, Gonschor, Bernhard, Herbolzheimer, Marit, Keppler, Lena, Hecker, Matthias, Reichert, Martin, Sander, Michael, Schmidt, Götz, Schneck, Emmanuel, Kleeff, Jorg, Lorenz, Kerstin, Ronellenfitsch, Ulrich, Thomssen, Christoph, Dumpies, Christian W., Fischer, Isabel, Gessner, Michael, Klauke, Friederike, Schmidt, Birte, Vinz, Franziska, Sander, Johannes, Betz, Christian Stephan, Bewarder, Julian, Burg, Simon, Klatte, Till Orla, König, Daniela, Köpke, Leon-Gordian, Stangenberg, Martin, Roux, Frederic, Hakami, Ibrahim Abdullah, Mall, Julian W, Graeb, Christian, Huber-Strößner, Kristin, Pempe, Christina, Kelly, Kathrin, Siebert, Julia, Agrawal, Rachit, Gousias, Konstantinos, Qureischie, Homeira, Meyer, Frank, Rissmann, Anke, Turial, Salmai, Al-Nawas, Bilal, Battista, Marco Johannes, Heider, Julia, Mueller, Lena Katharina, Jentschura, Sina- Louisa Patrizia, Kowalewski, Karl-Friedrich, Rassweiler-Seyfried, Marie-Claire, Reissfelder, Christoph, Rotter, Nicole, Scherl, Claudia, Seyfried, Steffen, Fichter, Andreas, Gempt, Jens, Schäffer, Christoph, Wegmann, Helmut, Aghamaliyev, Ughur, Böcker, Wolfgang, von Ehrlich-Treuenstätt, Viktor H., Ladurner, Roland, Schlager, Justin Gabriel, Smolka, Wenko, Glowalla, Claudio, Schneidmueller, Dorien, Henkel, Karl Wilhelm, Stadler, Josef, Hölz, Katharina, Brunner, Stefan M., Prantl, Lukas, Herzberg, Jonas, Kröger, Marie, Niemeier, Andreas, Sras, Yara, Reinhard, Tobias, Löffler, Markus W., Steidle, Christoph, Dayan, Davut, Greve, Jens, Löbig, Niklas, Schochter, Fabienne, Wezel, Felix, Pusch von, Silke, Schmidbauer, Stefan, Boenicke, Lars, Degener, Stephan, Seiberth, Rose, Smit, Marieke, von Rundstedt, Friedrich-Carl, Germer, Christoph-Thomas, Lock, Johan, Lotz, Christopher, Schlesinger, Tobias, Schmid, Benedikt, Treutlein, Agnes, Agyeman-Duah, Nana Kwaku, Appiah, Enoch, Gakpetor, Delali, Minlah Allah, Stephen, Adu-Aryee, Nii Armah, Agboadoh, Nelson, Bediako Bowan, Antoinette, Brown, George Darko, Clegg-Lamptey, Joe-Nat, Fenu, Benjamin Sena, Kumassah, Philemon, Hussey, Romeo, Agbeno, Evans Kofi, Amoako-Boateng, Mabel, Debrah, Samuel, Doku, Dr Kingsley, Mensah, Philip, Nortey, Michael, Opandoh, Isabella Naa Morkor, Yigah, Makafui, Jiagge, Nuna, Acquaye, Jane, Agyemang-Prempeh, Akosua, Amo-Antwi, Kwabena, Amoah, Michael, Amoah, George, Aning, Daniel Gyawu, Annor Mintah, Dominic, Arthur, Joshua, Darko- Asante, Regina, Gaveh, Valerie, Gyamfi, Frank Enoch, Jonathan, Boakye - Yiadom, Konney, Thomas Okpoti, Kyei, Ishmael, Nimako, Boateng, Ofosu-Barko, Ben Blay, Osabutey, Anita, Sagoe, Robert, Yifieyeh, Abiboye, Ansong, George, Abdul-Mumin, Alhassan, Amadu, Munira, Azahares Leal, German, Buunaaim, Alexis, Cheyuo, Ernest, Daboo Salifu, Latif, Issaka, Adamu, Yakubu, Musah, Grypiotis, Ioannis, Papadopoulou, Triada, Korkolis, Dimitrios, Thomakos, Nikolaos, Dellaportas, Dionysios, Dimitra, Papalouka, Hadjizacharias, Theodoros, Konstadoulakis, Manousos, Massaras, Dimitrios, Vezakis, Antonios, Avgerinos, Konstantinos, Kechagias, Aristotelis, Ioannidis, Argyrios, Patelis, Nikolaos, Deskou, Eirini, Stamos, Nikolaos, Tasis, Nikolaos, Danias, Nikolaos, Selmani, Jonida, Kalamatianos, Theodosis, Stranjalis, George, Kondilis, Panagiotis, Kanellopoulou, Vasiliki, Larentzakis, Andreas, Papanikolaou, Vasileios, Potamianos, Spyridon, Triantafyllou, Tania, Panagiotou, Peter, Avramidis, Emmanouil, Bessias, Nikolaos, Tsiantoula, Paraskevi, Charalabopoulos, Alexandros, Kykalos, Stylianos, Kyros, Eleandros, Machairas, Nikolaos, Mastoraki, Aikaterini, Papalampros, Alexandros, Terras, Alexis, Tsourouflis, Gerasimos, Zografos, Constantinos, Antzaka, Christina, Falara, Areti, Perreas, Konstantinos, Rellia, Panagiota, Tasouli, Androniki, Skolarikos, Andreas, Tzelves, Lazaros, Theodorakis, Emmanuel, Karona, Paraskevi, Tzouganakis, Angelos, Chrysos, Emmanuel, Nikolouzakis, Taxiarchis, Tourountzi, Paraskevi, Al, Aggeliki, Kalfountzos, Christos, Arnaoutoglou, Eleni, Christodoulidis, Gregory, Gkolias, Nick, Hajiioannou, Jiannis, Krestinidis, Giorgos, Ntalouka, Maria, Saini, Fani, Skoulakis, Charalampos, Terzoudis, Christos Dimitrios, Zacharoulis, Dimitris, Δακής, Κωνσταντίνος, Filo, Eva, Kontopoulou, Konstantina, Patoulias, Ioannis, Astreidis, Ioannis, Christidis, Panagiotis, Loutzidou, Lydia, Mantevas, Antonis, Tatsis, Dimitris, Tsakiridis, Ioannis, Iordanidou, Eirini, Brolo, Estuardo, Gutiérrez Ruiz, Alitza, De León Lima, María Alejandra, Flores, Mario-Andrés, Morales, Steffanía, Rivera, Pablo, Rodas, Lesly, Santos, Victor, Sosa, Dianne, Barrios Duarte, Amalia, Talé-Rosales, Luis-Fernando, Villeda, Sergio Alejandro, Anicetti, Joshua, Lowey, Megan, Ardebol, Javier, Barillas, Kathia, Barillas, Sabrina, Recinos, Salvador, Hon, Sophie, Liu, Alex Qinyang, Liu, Shirley, Ip, Ho Wai, Mak, Brian, Mok, Chung Ying, Wong, Kiu Fung, Au-Yeung, Kit Ying, Chan, David Yuen Chung, Chiu, Wang Kei, Ho, Jacky Yan Kit, Kung, Janet Wui Cheung, Ling, Samuel Ka Kin, Lok, Hon Ting, Teoh, Jeremy Yuen-Chun, Wong, Randolph, Antal, Zsuzsanna, Bahrehmand, Kiarash, Sztipits, Tamás, Hidi, László, Piros, Laszlo, Rózsa, Balazs, Herczeg, György, Saftics, György, Kulcsicka-Gut, Judit, Sipos, Zsófia, Majmudar, Hardil, Madabhavi, Irappa, G S, Anitha, Kesarla, Venkatesh, Kumar Venkatappa, Sunil, P B, Hareesh, Shivashankar Chikkanayakanahalli, Santhosh, Sunil, Tanvi, Rajagopal, Niranjana, P L, Thirumanikandan, Mishra, Nitu, Wadhwani, Dr Rekha, Dhurwe, Ritika, Pushpalatha, Kameshwarachari, Raj, Sumit, Singh, Pooja, Kumar, Pankaj, Mittal, Yash, Panigrahi, Sibasish, Parija, Sucheta, Patra, Saroj, Sahu, Rabi, Sultania, Mahesh, Tripathy, Sujit, Kansay, Rajeev, Gupta, Sunil Kumar, Kaman, Lileswar, Salunke, Pravin, Singh, Kavindra, Rela, Mohamed, Goudar, Swati, B, Barani kumar P, Murugesan, Anandan, Subbian, Anbukkani, Kumar, Arvind, Chauhan, Tapan singh, Govil, Akhil, Gupta, Shubhra, Sharma, Ashish, Tiwari, Saurabh, Vishwani, Vartika, Evelyn. R, Nissi, Deb, Mainak, Jayaram, Harish, Nagpal, Pooja, Pathak, Prachi, Choudhary, Gautam Ram, Chugh, Ankita, Elhence, Abhay, Madduri, Vijay, Pandey, Himanshu, Saxena, Rahul, Sharma, Naveen, Shekhar, Shashank, Vishnoi, Jeewan Ram, Bhende, Vishal, Chatterjee, Debarshi, Ghosh, Indranil, Naskar, Upasana, Jain, Prateek, Jain, Deepak, Kewlani, Vishal, Priya, Noopur, Parijat, Anand, Anand, Akshay, Bajaj, Ankur, Chaurasia, Akhilanand, Enny, Loreno E., Kumar, Ambrish, Mishra, Brijesh, Pandey, Amita, Rajan, Shiv, Roy, Ashutosh, Sachan, Rekha, Sankhwar, Pushp, Singh, Uma, Singh, Urmila, Srivastava, Chhitij, Verma, Manju Lata, Yadav, Awdhesh, Agarwal, Gaurav, Chanthar, K.m.m.vishvak, Hoysal, Dileep, Mishra, Anjali, Batra, Nitin, Bhatti, Arun, Dhar, Tapasya, Dutta, Rohini, Haque, Parvez David, Jain, Ritu, Luther, Anil, Mahajan, Amit, Pargal, Dr Pinki, Samuel, Abhishek, Singh, Inderjot, Singh Grewal, Sarvpreet, Singhania, Anusha, Alexander, Philip, Thomas, Josy, Krishna, Sunil, Singh, Narinder, Agarwal, Sunny, Balasubramaniam, Srikant, Dharap, Satish, Mhamane, Rameshwar, Nirgude, Anand, Parab, Sandesh, Peswani, Amit, Sahu, Anjana, Samel, Sarika, Shah, Fagun, Abraham, Bejoy, Asari, Ashishkumar, Badhe, Vivek, Badhwar, Sanjiv, Bothara, Vipul, Dalal, Anuj, Date, Avinash, Deshpande, Mandar, Doshi, Anirudha, Gade, Maya, Gajjar, Shreyash, Ghugare, Dr bhavisha, Jain, Divakar, Jenasamant, Saumya Sekhar, Joshi, Vinay, Kalwadia, Neha, Kayal, Akshat, Kulkarni, Yogesh, Mistry, Rajesh, Mulchandani, Manoj, Parab, Dr. Mrunal, Pednekar, Abhinav, Rahmani, Faizan, Rajput, Sunil, Sandlas, Gursev, Sarkar, Hrishikesh, Shetty, Sanket sadanand, Shukla kulkarni, Anshumala, Thete, Raghavendraswami, Wasnik, Shruti, Dhumane, Parag, Sharma, Rahul Deo, Deshmukh, Anuja, Gupta, Stuti, Nayak, Prakash, Thiagarajan, Shivakumar, Tiwari, Virendra Kumar, Voppuru, Saiesh Reddy, Soni, Rajesh, Bajpai, Minu, Farooque, Kamran, Parshad, Rajinder, Sharma, Vijay, Bansal, Kuldeep, Bains, Lovenish, Bhardwaj, Rohit, Mittal, Abhishek, Ponnusamy, Sabarirajan, Ghodke, Rahul, Himani, Kumar, Ashwani, Gadekar, Anup, Panjwani, Taufiq, Maji, Suvendu, Basu, Somprakas, Kandwal, Pankaj, Kumar, Shashank, Poonia, Dharma Ram, Sadhasivam, Saravanan, Mahakalkar, Chandrashekhar, Choudhury, Yousuf, Das, Devishmita, Goala, Subhadra, Singha, S Thoibisana, Singha, Damayanti, Mehraj, Asif, Parray, Fazl, Shah, Raahil, Wani, Rauf, Hegde, Siddhi, Ankadavar, Dr.sushil, Bafna, Darshan, Lad, Parag, Chisthi, Meer, Jothi, Harihara, .C. Mathew, Godwin David, Abel, Livingston, Barla, Ravi Kishore, Benjamin, Santosh, Bliss, Jeremy, Ete, Geley, James, Deeptiman, Jesudason, Mark Ranjan, Karnan, Gomathi, Mark Samuel, Vasanth, Mittal, Rohin, Nathan, Senthil K, Selvaraj, Daniel, Surendran, Suraj, T D, Hariharan, Thangaraj, Santhosh Kumar, Thomas, Varghese, Dilmy, Mohammad Adya Firmansha, Pratama, Dedy, Sugiarto, Adhrie, Surya, Ilham Utama, Tango, Tamara, Hasyim, Andi, Susanti, Ade, Saputra, Teddy, Syarifuddin, Erwin, Islam, Andi Asadul, Anam, Khoirul, Sugianto, Julius Albert, Lestari, Mayang Indah, Amba, Erick Gamaliel, Apriawan, Tedy, Wathoni, Roidah Taqiyya Zahra, Widyastuti, Yunita, Yun Jufan, Akhmad, Etezadpour, Mohammad, Mehrad-Majd, Hassan, Rajaei, Parisa, Mehdizadeh, Mohammad, Soltani, Mina, Pour, Ali Moazami, Azarnia, Gholamreza, Alizadeh, Narges, Mokarami, Hossein, Tehrani, Shahrzad, Alborzi, Majid, Bagheri, Hamed, Eshraghi, Mohsen, Fatemi manesh, Hassan, Hejazi, Seyed fakhreddin, Pezeshki Modarres, Mahdi, Shafiee, Ali, Vafaeimanesh, Jamshid, Hosseini, Elahe, Nikoupour, Hamed, Bastaninejad, Shahin, Firouzifar, Mohammadreza, Motasaddi zarandy, Masoud, Yazdani, Nasrin, Yousefzadeh Kandevani, Naser, Mortazavi, SM Javad, Ahmadi, Sayedali, Khosravi, Mohammad Hossein, Vosoughi, Fardis, Golbakhsh, Mohammadreza, Al-Isawi, Ali, Al-Masood, Mohammed, Gahtan, Yarub, Ahmed, Abdullah, Hilmi, Ahmed, Muhssein, Haidar, McNestry, Catherine, Ekwere, Bosom, Essajee, Murtaza, Chan Chin, Bruno, Edwards Murphy, Amy, Fleming, Christina, Foley, Niamh, Gardiner, Padraig, Hechtl, Daniel, Kayyal, Mohd yasser, Lyons, Maria, O’Brien, Stephen, Ng, Mei Yee, Oduola, Oladayo, Aljohmani, Lylas, Nugent, Timothy, Harris, Johnathon, Kearney, David, Keenan, Robert Anthony, Nolan, Deirdre, Salloum, Croghan, Stefanie M, Donohoe, Emma, Larkin, John, Lynch, Thomas Hugh, Manecksha, Rustom, Nagassima, Katharina, Barry, Mary, Cullinane, Carolyn, Dowdall, Joseph, Hurson, Conor, Kelly, Orlaith, Kennelly, Rory, Kiernan, Aoife, Murphy, Ben, Njeze, Nwabundo, Reynolds, Ian Sean, Winter, Des, Ravi, Akshaya, Ridgway, Paul, Fowler, Amy, McAnena, Peter, Bahadoor, Muhammad Usaama, Kabir, Syed Mohammad Umar, Khalid, Mohamed Hamed, Mujtaba, Syed Nadeem, Sarwar, Muhammad assam, Sugrue, Michael, Varzgalis, Manvydas, Jones-Whiting, Larne, Lim, Seantee, Ryan, Éanna, Sara, Al-Mukhaizeem, Youssef, Crowley, Clare, Flanagan, Michael, Fogarty, Amy, Glynn, Orna, Hill, Rhodri, Khalid, Muhammad Abdullah, Majeed, Zubair, McCullough, Peter, Neary, Peter, Noone, Anthony, O’Kelly, John, Abu abed, Arsan, Haim, Nadav, Hershkovitz, Yehuda, Majadla, Omar, Rabin, Igor, Zmora, Osnat, Demma, Yonatan Avraham, Fishman, Yuri, Farkas, Amicur, Gozal, Yaacov, Greenman, Dmitry, Ostrovsky, Israel Alexander, Pardes, Rivka, Shahar, Tal, Teren, David, Yahud, Reuven, Yellinek, Shlomo, Cianci, Pasquale, Minafra, Marina, Restini, Enrico, Bussolin, Edoardo, De Prizio, Marco, Sulce, Rezart, Poiasina, Elia, Antonacci, Filippo, Arena, Alessandro, Belvedere, Angela, Bernagozzi, Fabio, Boussedra, Safia, Cescon, Matteo, Cipolli, Alessandro, Daddi, Niccolo’, De Crescenzo, Eugenia, De Iaco, Pierandrea, Del Gaudio, Massimo, Della Gatta, Anna Nunzia, Droghetti, Matteo, Giorgini, Federico A., Lanci Lanci, Antonio, Masetti, Michele, Minni, Francesco, Morezzi, Daniele, Perrone, Anna Myriam, Pignatti, Marco, Puglisi, Silvana Bernadetta, Rottoli, Matteo, Schiavina, Riccardo, Serenari, Matteo, Serra, Margherita, Tesei, Marco, Violante, Tommaso, Aspide, Raffaele, Carretta, Alessandro, Conti, Alfredo, De Vita, Carla, Friso, Filippo, La Corte, Emanuele, Rosetti, Vittoria, Sturiale, Carmelo, Donati, Davide Maria, Palmerini, Emanuela, Berselli, Bruno, Bolognesi, Silvia, Farnia, Francesco, Maremonti, Pietro, Razzaboni, Alessandra, La Mendola, Roberta, Arrigoni, Giulia, Baiocchi, Gian Luca, Molfino, Sarah, Panciani, Pier Paolo, Sartori, Enrico, Zanin, Luca, Perrone, Fabrizio, Cappellani, Alessandro, Giaquinta, Alessia, Gioco, Rossella, Veroux, Pierfrancesco, Cianci, Antonio, Lo Giudice, Arturo, Russo, Giorgio Ivan, Sarpietro, Giuseppe, Scandura, Carmen Emanuela, Barca, Ida, Carnevali, Adriano, De Paola, Gilda, Giannaccare, Giuseppe, Sammarco, Giuseppe, D’Andrea, Marcello, Tosatto, Luigino, Mucilli, Felice, Muraglia, Angelo, Giuliani, Domenico Benvenuto, Segalini, Edoardo, Daniele, Alberto, Gelarda, Enrico, Olearo, Elena, Puppo, Andrea, Testa, Valentina, Porta, Andrea, Birindelli, Arianna, Bernabei, Massimiliano, Feo, Carlo V., Virgilio, Edoardo, Bartolini, Ilenia, Bottari, Andrea, Checcucci, Carlotta, De Vincenti, Rosita, Fambrini, Massimiliano, Fortuna, Laura, Gallo, Oreste, Maltinti, Gherardo, Taddei, Antonio, Michelagnoli, Stefano, Maccagnano, Giuseppe, Pesce, Vito, Ercolani, Giorgio, Fappiano, Francesca, Barberis, Andrea, Filauro, Marco, Santoliquido, Matteo, Aprile, Alessandra, Barra, Fabio, De Rosa, Raffaele, Ferrero, Simone, Sparavigna, Marco, Vagge, Aldo, Gambardella, Denise, Tedesco, Manfredo, Spampinato, Marcello Giuseppe, Chiarelli, Marco, Grandi, Samuele, Lenzi, Riccardo, Muscatello, Luca, Germano’, Antonino Francesco, Giani, Alessandro, Bissacco, Daniele, Cassinotti, Elisa, Pignataro, Lorenzo, Torretta, Sara, Armellin, Daniele, Basato, Silvia, Carrano, Francesco Maria, Colombo, Giovanni, De Lucia, Francesca, De Virgilio, Armando, Ferreli, Fabio, La Raja, Carlotta, Milana, Flavio, Rossi, Vanessa, Russo, Elena, Tamburello, Sara, Zerbi, Alessandro, Bona, Davide, Adamoli, Laura, Ansarin, Mohssen, Chu, Francesco, De Berardinis, Rita, Pietrobon, Giacomo, Sedda, Giulia, Caputo, Maria, Cellerino, Paola, Crespi, Michele Achille, Danelli, Piergiorgio, Ferrara, Francesco, Baccellieri, Domenico, Candiani, Massimo, Casiraghi, Arianna, Cipriani, Federica, De Nardi, Paola, Mortini, Pietro, Nocera, Gianluca, Pozzoni, Mirko, Ruffolo, Alessandro Ferdinando, Spina, Alfio, Barberio, Cristina, Beretta, Luigi, Cavenago, Francesca, Fresilli, Stefano, Landoni, Giovanni, Lombardi, Gaetano, Bonomi, Stefano, Guaglio, Marcello, Sala, Laura, Segattini, Silvia, Piccoli, Micaela, Migliore, Marco, Sasia, Diego, Cereda, Marco, Dell’Oro, Cristina, Fogliati, Alessandro, Tamini, Nicolò, Castaldi, Antonio, Bracale, Umberto, Lionetti, Ruggero, Pagano, Gianluca, Peltrini, Roberto, Pirozzi, Nello, D’amico, Maria, Izzo, Francesco, Marra, Ester, Marte, Gianpaolo, Bianco, Francesco, Cappiello, Antonio, Iovino, Claudio, Menna, Maria Paola, Romano, Francesco maria, Rossi, Settimio, Sciaudone, Guido, Ascari, Francesca, Bellora, Paolo, Cerri, Cristina, D’Aloisio, Giordana, Ferrari, Maurizio, Chioffi, Franco, Ciccarino, Pietro, Nezi, Giulia, Bissolotti, Guido, Di Donna, Mariano Catello, Licari, Leo, Salamone, Giuseppe, Toia, Francesca, Annicchiarico, Alfredo, Berretta, Roberto, Capozzi, Vito Andrea, Freyrie, Antonio, Frusca, Tiziana, Arici, Vittorio, Bozzani, Antonio, Filardo, Matteo, de Manzoni Garberini, Andrea, Cauteruccio, Michele, Caristo, Giuseppe, Calabrò, Marcello, Andreani, Lorenzo, Antonio, D’arienzo, Berrettini, Stefano, Colangeli, Simone, Cremonini, Camilla, Dallan, Iacopo, Di Franco, Gregorio, Korasidis, Stylianos, Musetti, Serena, Neri, Carlo Maria, Palmeri, Matteo, Picariello, Miriana, Statuti, Erica, Tartaglia, Dario, Pinotti, Enrico, Basso, Stefano Maria Massimiliano, Ubiali, Paolo, Coiro, Saverio, Mele, Simone, Corbellini, Carlo, Masciandaro, Antonio, Carannante, Filippo, Denaro, Vincenzo, Mazzotta, Erica, Zampogna, Biagio, Cinquepalmi, Matteo, Del Basso, Celeste, Guglielmo, Nicola, Meniconi, Roberto Luca, Sinibaldi, Giovanni, Agnes, Annamaria, Belia, Francesco, Bianchi, Valentina, Cozza, Valerio, Fico, Valeria, Fransvea, Pietro, La Greca, Antonio, Litta, Francesco, Pascale, Marco Maria, Silvia, Tedesco, Benevolo, Maria, Campo, Flaminia, Dona’, Maria Gabriella, Marchesi, Paolo, Mastroianni, Riccardo, Mazzola, Francesco, Moretto, Silvia, Petruzzi, Gerardo, Pichi, Barbara, Tuderti, Gabriele, Bellato, Vittoria, Grande, Michele, Petagna, Lorenzo, Sensi, Bruno, Bruzzaniti, Placido, Ciccarone, Flavia, Cicerchia, Pierfranco Maria, Cirillo, Bruno, D’ambrosio, Giancarlo, De Toma, Giorgio, Familiari, Pietro, Fonsi, Giovanni Battista, Pata, Francesco, Picchetto, Andrea, Salvati, Maurizio, Valentini, Valentino, Zambon, Martina, Zancana, Giuseppa, Zuppi, Emma, Ibrahim, Mohsen, Menna, Cecilia, Rendina, Erino Angelo, Accarino, Giulio, Giancarlo, Accarino, Froiio, Caterina, Copelli, Chiara, Di Maio, Pasquale, Giudice, Marco, Altana, Cristian, Ciccarello, Sandro, Cossu, Maria Laura, Dessole, Francesco, Dettori, Salvatora, Madonia, Massimo, Petrillo, Marco, Piredda, Franco, Rizzo, Davide, Scognamillo, Fabrizio, Soma, Damiano, Tanca, Anna Rita, Marano, Luigi, Pesce, Anna Lisa, Piccioni, Stefania Angela, Resca, Luca, Roviello, Franco, Abrate, Alberto, Clarizia, Guglielmo, Franzini, Marco, Fratto, Antonio, Grechi, Alessandro, Scarnecchia, Elisa, Maiuri, Vincenzo, Dalprà, Francesca, Battistella, Enrico, Romano, Maurizio, Aizza, Giada, de Manzini, Nicolò, Drigo, Davide, Mastronardi, Manuela, Palmisano, Silvia, Bardelli, Laura, Borroni, Giacomo, Livraghi, Lorenzo, Palumbo, Mara, Zullo, Alessandra, Vignotto, Chiara, Caravati, Andrea, De Cristofaro, Carlotta, Giuliani, Tommaso, Guglielmi, Alfredo, Pedrazzani, Corrado, Butturini, Giovanni, Moretto, Gianluigi, Mastriale, Francesco, Olmi, Stefano, Kushikata, Tetsuya, Oyama, Tasuku, Kamiyama, Mizue, Tarao, Kentaroh, Yamada, Takayuki, Shiga, Toshiya, Deguchi, Yoshihiko, Hoshino, Tatsuki, Inoue, Hiroyuki, Ito, Shingo, Takano, Emi, Yamamoto, Masae, Matsuki, Yuka, Matsumoto, Takashi, Sawada, Atsushi, Sato, Kozo, Makino, Jun, Mizota, Toshiyuki, Yonekura, Hiroshi, Ishikawa, Haruka, Kaiho, Yu, Ogawa, Munehiro, Endo, Shunji, Fujiwara, Yoshinori, Kubota, Hisako, Okada, Toshimasa, Hisamatsu, Yoji, Michiura, Taku, Satoshi, Okazaki, Fujita, Tomoyuki, Fukushima, Satsuki, Otsuka, Yuji, Sawada, Ikumi, Miyamoto, Morikazu, Isada, Tetsuro, Bani Amer, Qaed, Fujimoto, Yuki, Kuratani, Norifumi, Takada, Misa, Noro, Shusaku, Kuroda, Naoto, Okamura, Yukiyasu, Uesaka, Katshuhiko, Kuroda, Kento, Abe, Nobutsugu, Ando, Tadao, Hirano, Kouichi, Kobayashi, Yoichi, Motoyasu, Akira, Noguchi, Hikari, Tajima, Atsushi, Toyama, Satoshi, Uchida, Tokujiro, Furukawa, Yuri, Hasumi, Yoko, Iida, Katsuyuki, Ikeda, Tatsuhiko, Kuzuhara, Shigeki, Yamamoto, Naoya, Yamamoto, Mari, Yokota, Toshiya, Yoshioka, Yuki, Kawai, Akira, Nakata, Yoshinori, Sawamura, Shigehito, Kobayashi, Takayuki, Alqudah, Majdi Ali, Alrabadi, Mera, Owais, Qais, Smadi, Aseel, Abunawas, Huthifa, Alhawatmeh, Mohammad, Alwardat, Abdel Rahman Mohannad Ahmad, Dhoon, Slsabela, Jaradat, Enas, Mubaydeen, Teeba, Alzraikat, Sayel H., Omari, Rand Y., Suradi, Haya H., Al Abdallah, Murad, Al Bdour, Zakaria, Al-thaher, Mohammad, Alnajjar, Tareq, AlZaatreh, Mohammad, Ayasra, Faris, Ghayada, Ibrahim, Hasanein, Khaled Moh’d Ahmed, Hassouneh, Anas, Hijazeen, Raid, Khasawneh, Barihan, Semrin, Qusai, Theab, Mohammad, Abazeed, Alaa, Alkurdieh, Moh’d Mujahed, Hammouri, Mohammad, Khader, Sereen, Abu Obead, Hamza, Abudari, Hadeel, Al-azzeh, Nimer, Al-Darabah, Ali, Al-Qannas, Mohammad, Ashour, Subhi, Chabaan, Reem, Fawzi, Ahmad, Haij, Manal, Hassouneh, Esraa, Ibrahim, Zainab, Mohamed, Ishak, Qandeel, Mahmoud, Qassem, Faisal, Shorman, Marwan, Nofal, Sandra, Salameh, Mohammed, Sanjuq, Ghaidaa, Sharabi, Alaa, Sweiti, Alaa, Baninasr, Eman, Abuleil, Amro, Abou Chaar, Mohamad K., Al-latayfeh, Motasem, Al-Shudifat, Abdel-Ellah, Shaikh Ahmad, Abd Almonem, Abu Abed, Laith, Allouzi, Mohammad, Almi’ani, Sari, Alsaiad, Abdulhakim, Daoud, Maher, Dawod, Omar, Fadli, Saba, Jimaale, Elmi Ahmed Mohamed, Qulaghassi, Zaki, Al-howthi, Mohammed, Ababneh, Laila, Ababneh, Roba, Al Khassawneh, Ahmad, Al Sharie, Ahmed, Al-Dabaa, Tawfik, Al-Jarrah, Salsabeel, Alshannaq, Qutaiba, Alsulaiman, Rima, Audat, Ziad, Bdour, Saja, Khatatbeh, Ro’a, Marji, Fares, Abu Ismail, Dima.Y, Abu-Ismail, Luai, Alzoubi, Mai, Alzoubi, Malak, Hussein, Hasan, Rawashdeh, Shireen, Ababneh, Adnan, Abu-Eisheh, Basil, Al Shurman, Hana’, Al-atiyah, Hussam, Aljaiuossi, Anas, Hamdoni, Sara, Kulimbet, Mukhtar, Sakhov, Orazbek, Fakhradiyev, Ildar, Tanabayeva, Shynar, Zhussupov, Baurzhan, Amrayev, Sultan, Kukubassov, Yerlan, Parker, Robert, Mwaria, Claude, Kibunyi, Muthoni, Mailu, Claire, Osea, Lydia, Hirsi, Omar, Dashti, Mustafa, Aldalal, Shuaib, Alozairi, Ous, Al-Shaiji, Tariq, Alhunaidi, Omar, Aljewaied, Ali, Farag, Ahmed, Termos, Salah, Sivins, Armands, Apse, Ingus Arnolds, Kaminskis, Aleksejs, Pāvulāns, Jānis, Itani, Rania, Owiedat, Mustafa, Antonios, Ingrid, Milan Moussa, Rita, Abdel Sater, Ali H., Souleiman, Bassem, Ghiya, Peter, Fakih, Ghinwa, Tamoos, Khalil, Abdulrahman, Taha, Omar Abunaaja, Hayat, Al Gasi, Abd El Jawad, Al maadany, Faraj, Alsaeiti, Sara, Elkhafeefi, Fatimah, Alhouni, Tarek, Alkeelani, Hana, Alkuwafi, Rauoof, Elbargathe, Osama, Elfadli, Mustafa, Elmahgoub, Asma, Alansari, Arowa hassan abdulrahman, Alhaje, Awatif, Haron, Aaya, Alsuwiyah, Suhir, Khel, Samer, Yousef, Rowaida, Abuhlaiga, Ma’aly, Abushahma, Ahmed omar, Aldelensi Alzubi, Alhosen Saleh M, Alnehum, Mohamed alnaser, Alzedam, Ahmad, Matoug, Faisel, Mohammed, Burooj, Sawalem, Mohamed, Kamoka, Elhusain, Salamah, Abdulrauf, Abdeewi, Saedah, Eshnaf, Mabroka, Yahmad, Mohammad, Aljuroushi, Omar, Attia, Hajer, Emran, Ayyah, Samer, Ashraf, Abdullah, Duha milad, Ben esmael, Esraa, Benmasoud, Fatma, Debri, Laila, Younis, Balkees, Elmabrouk, Amna, Hasan, Ameerah Mahdi Abraheem, Suliaman, Taha, Alawami, Mohammed, Alshareea, Entisar, Aribi, Tomather, Lamari, Amani hamid, Mufth, Mohammed, Aburima, Sarah, Al shukri, Asmaa, Alarabi, Rehab, Alelwany, Aisha, Bashir, Rasha, Elhadi, Ahmed, Elkouba, Esraa, Ellojli, Ibrahim, Elmsherghi, Nabiha, Haidar, Arwa, Helal, Hala, Kriem, Eslam, Turshani, Laila, Alayan, Mohammed, Ben Hasan, Hayat, Shaban Ben Hasan, Najat, Shaban Ben Hasan, Rabab, Dambrauskas, Zilvinas, Dekeryte, Inga, Koženiauskaitė, Akvilė, Maleckas, Almantas, Venclauskas, Linas, Zilinskas, Justas, Syminas, Vilius, Aliosin, Oleg, 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Abstract: Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery.
Published: 2024
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35. Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Author: Jonathan Youngs, Nicholas M Provine, Nicholas Lim, Hannah R Sharpe, Ali Amini, Yi-Ling Chen, Jian Luo, Matthew D Edmans, Panagiota Zacharopoulou, Wentao Chen, Oliver Sampson, Robert Paton, William J Hurt, David A Duncan, Anna L McNaughton, Vincent N Miao, Susannah Leaver, Duncan L A Wyncoll, Jonathan Ball, Philip Hopkins, Oxford Immunology Network Covid-19 response T cell Consortium, Oxford Protective T cell Immunology for COVID-19 (OPTIC) Clinical team, Donal T Skelly, Eleanor Barnes, Susanna Dunachie, Graham Ogg, Teresa Lambe, Ian Pavord, Alex K Shalek, Craig P Thompson, Luzheng Xue, Derek C Macallan, Philip Goulder, Paul Klenerman, and Tihana Bicanic
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Published: 2021
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36. Isolated subcutaneous recurrence of high-grade neuroendocrine tumor of the cervix

Author: Lia Bos, Alison Goulder, Lauren Prescott, Mirna Podoll, Michael Frumovitz, and Alaina J. Brown
Subjects: Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2021
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37. Differential Escape Patterns within the Dominant HLA-B*57:03-Restricted HIV Gag Epitope Reflect Distinct Clade-Specific Functional Constraints

Author: Payne, RP, Branch, S, Kløverpris, H, Matthews, PC, Koofhethile, CK, Strong, T, Adland, E, Leitman, E, Frater, J, Ndung'u, T, Hunter, E, Haubrich, R, Mothe, B, Edwards, A, Riddell, L, Chen, F, Harrigan, PR, Brumme, ZL, Mallal, S, John, M, Jooste, JP, Shapiro, R, Deeks, SG, Walker, BD, Brander, C, Landis, C, Carlson, JM, Prado, JG, and Goulder, PJR
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Vaccine Related, Genetics, Sexually Transmitted Infections, HIV/AIDS, Clinical Research, Immunization, 2.1 Biological and endogenous factors, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Adult, Cohort Studies, Epitopes, Female, Genotype, HIV Infections, HLA-B Antigens, Humans, Immune Evasion, Male, Middle Aged, Mutation, Missense, Selection, Genetic, T-Lymphocytes, Cytotoxic, gag Gene Products, Human Immunodeficiency Virus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract: UnlabelledHLA-B*57:01 and HLA-B*57:03, the most prevalent HLA-B*57 subtypes in Caucasian and African populations, respectively, are the HLA alleles most protective against HIV disease progression. Understanding the mechanisms underlying this immune control is of critical importance, yet they remain unclear. Unexplained differences are observed in the impact of the dominant cytotoxic T lymphocyte (CTL) response restricted by HLA-B*57:01 and HLA-B*57:03 in chronic infection on the Gag epitope KAFSPEVIPMF (KF11; Gag 162 to 172). We previously showed that the HLA-B*57:03-KF11 response is associated with a >1-log-lower viral setpoint in C clade virus infection and that this response selects escape mutants within the epitope. We first examined the relationship of KF11 responses in B clade virus-infected subjects with HLA-B*57:01 to immune control and observed that a detectable KF11 response was associated with a >1-log-higher viral load (P = 0.02). No evidence of HLA-B*57:01-KF11-associated selection pressure was identified in previous comprehensive analyses of >1,800 B clade virus-infected subjects. We then studied a B clade virus-infected cohort in Barbados, where HLA-B*57:03 is highly prevalent. In contrast to findings for B clade virus-infected subjects expressing HLA-B*57:01, we observed strong selection pressure driven by the HLA-B*57:03-KF11 response for the escape mutation S173T. This mutation reduces recognition of virus-infected cells by HLA-B*57:03-KF11 CTLs and is associated with a >1-log increase in viral load in HLA-B*57:03-positive subjects (P = 0.009). We demonstrate functional constraints imposed by HIV clade relating to the residue at Gag 173 that explain the differential clade-specific escape patterns in HLA-B*57:03 subjects. Further studies are needed to evaluate the role of the KF11 response in HLA-B*57:01-associated HIV disease protection.ImportanceHLA-B*57 is the HLA class I molecule that affords the greatest protection against disease progression in HIV infection. Understanding the key mechanism(s) underlying immunosuppression of HIV is of importance in guiding therapeutic and vaccine-related approaches to improve the levels of HIV control occurring in nature. Numerous mechanisms have been proposed to explain the HLA associations with differential HIV disease outcome, but no consensus exists. These studies focus on two subtypes of HLA-B*57 prevalent in Caucasian and African populations, HLA-B*57:01 and HLA-B*57:03, respectively. These alleles appear equally protective against HIV disease progression. The CTL epitopes presented are in many cases identical, and the dominant response in chronic infection in each case is to the Gag epitope KF11. However, there the similarity ends. This study sought to better understand the reasons for these differences and what they teach us about which immune responses contribute to immune control of HIV infection.
Published: 2014

38. Mapping the drivers of within-host pathogen evolution using massive data sets

Author: Duncan S. Palmer, Isaac Turner, Sarah Fidler, John Frater, Dominique Goedhals, Philip Goulder, Kuan-Hsiang Gary Huang, Annette Oxenius, Rodney Phillips, Roger Shapiro, Cloete van Vuuren, Angela R. McLean, and Gil McVean
Subjects: Science
Abstract: Various host factors may impact within-host pathogen evolution. Here, the authors develop a Bayesian approach for identifying host-pathogen interactions using large data sets of pathogen diversity, and apply it to investigate HLA-induced selection in the HIV-1 genome.
Published: 2019
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39. HBV vaccination and PMTCT as elimination tools in the presence of HIV: insights from a clinical cohort and dynamic model

Author: Anna L. McNaughton, José Lourenço, Louise Hattingh, Emily Adland, Samantha Daniels, Anriette Van Zyl, Connie S. Akiror, Susan Wareing, Katie Jeffery, M. Azim Ansari, Paul Klenerman, Philip J. R. Goulder, Sunetra Gupta, Pieter Jooste, and Philippa C. Matthews
Subjects: Hepatitis B virus, Epidemiology, Africa, Antibodies, Immunisation, PMTCT, Medicine
Abstract: Abstract Background Sustainable Development Goals set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Deployment of a robust prophylactic vaccine and enhanced interventions for prevention of mother to child transmission (PMTCT) are cornerstones of elimination strategy. However, in light of the estimated global burden of 290 million cases, enhanced efforts are required to underpin optimisation of public health strategy. Robust analysis of population epidemiology is particularly crucial for populations in Africa made vulnerable by HIV co-infection, poverty, stigma and poor access to prevention, diagnosis and treatment. Methods We here set out to evaluate the current and future role of HBV vaccination and PMTCT as tools for elimination. We first investigated the current impact of paediatric vaccination in a cohort of children with and without HIV infection in Kimberley, South Africa. Second, we used these data to inform a new parsimonious model to simulate the ongoing impact of preventive interventions. By applying these two approaches in parallel, we are able to determine both the current impact of interventions, and the future projected outcome of ongoing preventive strategies over time. Results Existing efforts have been successful in reducing paediatric prevalence of HBV infection in this setting to
Published: 2019
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40. Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes

Author: Mann, Jaclyn K, Byakwaga, Helen, Kuang, Xiaomei T, Le, Anh Q, Brumme, Chanson J, Mwimanzi, Philip, Omarjee, Saleha, Martin, Eric, Lee, Guinevere Q, Baraki, Bemuluyigza, Danroth, Ryan, McCloskey, Rosemary, Muzoora, Conrad, Bangsberg, David R, Hunt, Peter W, Goulder, Philip JR, Walker, Bruce D, Harrigan, P, Martin, Jeff N, Ndung’u, Thumbi, Brockman, Mark A, and Brumme, Zabrina L
Abstract: Abstract Background The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef’s most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. Results Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naïve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation.
Published: 2013

41. Influence of HLA-C Expression Level on HIV Control

Author: Apps, Richard, Qi, Ying, Carlson, Jonathan M, Chen, Haoyan, Gao, Xiaojiang, Thomas, Rasmi, Yuki, Yuko, Del Prete, Greg Q, Goulder, Philip, Brumme, Zabrina L, Brumme, Chanson J, John, Mina, Mallal, Simon, Nelson, George, Bosch, Ronald, Heckerman, David, Stein, Judy L, Soderberg, Kelly A, Moody, M Anthony, Denny, Thomas N, Zeng, Xue, Fang, Jingyuan, Moffett, Ashley, Lifson, Jeffrey D, Goedert, James J, Buchbinder, Susan, Kirk, Gregory D, Fellay, Jacques, McLaren, Paul, Deeks, Steven G, Pereyra, Florencia, Walker, Bruce, Michael, Nelson L, Weintrob, Amy, Wolinsky, Steven, Liao, Wilson, and Carrington, Mary
Subjects: Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Genetics, Sexually Transmitted Infections, Infectious Diseases, Clinical Research, HIV/AIDS, Cancer, 2.1 Biological and endogenous factors, Aetiology, Infection, Inflammatory and immune system, Black or African American, Alleles, Amino Acid Sequence, Anti-Retroviral Agents, Crohn Disease, Gene Expression Regulation, HIV, HIV Infections, HLA-C Antigens, Humans, Immunodominant Epitopes, Molecular Sequence Data, Mutation, Peptide Fragments, Polymorphism, Single Nucleotide, T-Lymphocytes, Cytotoxic, Viral Load, General Science & Technology
Abstract: A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.
Published: 2013

42. Definition of the viral targets of protective HIV-1-specific T cell responses

Author: Mothe, Beatriz, Llano, Anuska, Ibarrondo, Javier, Daniels, Marcus, Miranda, Cristina, Zamarreño, Jennifer, Bach, Vanessa, Zuniga, Rosario, Pérez-Álvarez, Susana, Berger, Christoph T, Puertas, Maria C, Martinez-Picado, Javier, Rolland, Morgane, Farfan, Marilu, Szinger, James J, Hildebrand, William H, Yang, Otto O, Sanchez-Merino, Victor, Brumme, Chanson J, Brumme, Zabrina L, Heckerman, David, Allen, Todd M, Mullins, James I, Gómez, Guadalupe, Goulder, Philip J, Walker, Bruce D, Gatell, Jose M, Clotet, Bonaventura, Korber, Bette T, Sanchez, Jorge, and Brander, Christian
Abstract: Abstract Background The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. Methods Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. Results For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. Conclusions The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.
Published: 2011

43. Corrigendum: Cytomegalovirus-Mediated T Cell Receptor Repertoire Perturbation Is Present in Early Life

Author: Meriem Attaf, Julia Roider, Amna Malik, Cristina Rius Rafael, Garry Dolton, Andrew J. Prendergast, Alasdair Leslie, Thumbi Ndung’u, Henrik N. Kløverpris, Andrew K. Sewell, and Philip J. Goulder
Subjects: cytomegalovirus, T cell receptor, T cell receptor repertoire, superdominance, paediatric repertoire, repertoire dynamics, Immunologic diseases. Allergy, RC581-607
Published: 2020
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44. Distinct Immunoglobulin Fc Glycosylation Patterns Are Associated with Disease Nonprogression and Broadly Neutralizing Antibody Responses in Children with HIV Infection

Author: M. Muenchhoff, A. W. Chung, J. Roider, Anne-Sophie Dugast, Simone Richardson, Henrik Kløverpris, Alasdair Leslie, Thumbi Ndung’u, Penny Moore, Galit Alter, and Philip J. R. Goulder
Subjects: Fc effector functions, Fc glycosylation, HIV, broadly neutralizing antibodies (bnAbs), nonneutralizing antibodies, pediatric, Microbiology, QR1-502
Abstract: ABSTRACT A prophylactic HIV vaccine would ideally induce protective immunity prior to sexual debut. Children develop broadly neutralizing antibody (bnAb) responses faster and at higher frequencies than adults, but little is known about the underlying mechanisms or the potential role of Fc-mediated effector functions in disease progression. We therefore performed systems immunology, with immunoglobulin profiling, on HIV-infected children with progressive and nonprogressive disease. Pediatric nonprogressors (PNPs) showed distinct immunoglobulin profiles with an increased ability to elicit potent Fc-mediated natural killer (NK)-cell effector functions. In contrast to previous reports in adults, both groups of children showed high levels of gp120-specific IgG Fc glycan sialylation compared to bulk IgG. Importantly, higher levels of Fc glycan sialylation were associated with increased bnAb breadth, providing the first evidence that Fc sialylation may drive affinity maturation of HIV-specific antibodies in children, a mechanism that could be exploited for vaccination strategies. IMPORTANCE To protect future generations against HIV, a vaccine will need to induce immunity by the time of sexual debut and hence requires immunization during childhood. Current strategies for a prophylactic HIV vaccine include the induction of a broadly neutralizing antibody response and the recruitment of potent effector functions of immune cells via the constant antibody Fc region. In this study, we show that nonprogressing HIV-infected children mounted antibody responses against HIV that were able to mediate potent Fc effector functions, which may contribute to the control of HIV replication. Children who had specific glycan structures on the Fc portion of antibodies against HIV were able to neutralize a broader range of HIV variants, providing evidence of a potential role of Fc glycovariation in the development of bnAbs against HIV. These findings complement our knowledge of the distinct immune landscape in early life that could be exploited in the development of vaccine strategies.
Published: 2020
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45. In silico veritas? Potential limitations for SARS-CoV-2 vaccine development based on T-cell epitope prediction.

Author: Sandra Silva-Arrieta, Philip J R Goulder, and Christian Brander
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Published: 2020
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46. Management and early outcomes of children with appendicitis in the UK and Ireland during the COVID-19 pandemic: a survey of surgeons and observational study

Author: Nigel J Hall, Vivek Gupta, Anna-may Long, Nuha Yassin, Alan Askari, David Colvin, Stewart Cleeve, Arun Kelay, Chris Driver, Clare Rees, Eleri Cusick, Hetal Patel, Ingo Jester, Khalid Elmalik, Sean Marven, Tim Bradnock, Oliver Brown, Andrew Jackson, Richard Egan, Laura Phillips, Marianne Hollyman, Bankole Oyewole, Fenella Welsh, Dale Vimalachandran, Melissa Gabriel, Kate Cross, Iain Yardley, Mark Peter, Andrew Beamish, Sophie Lewis, Milan Gopal, Joshua McIntyre, Merrill McHoney, Ionica Stoica, Hany Gabra, Tristan Boam, Angeliki Kosti, Katie cross, Andrew Mitchell, Michael Terry, George S Bethell, Clare M Rees, Jonathan R Sutcliffe, Florin Djendov, Victor Emordi, Sarah Staight, Christina Major, Oscar Croysdale, Mike Nelson, Hannah Rhodes, Juliette King, Gillian Winter, Selena Curkovic, Raef Jackson, Bhushanrao Jadhav, Thomas Raymond, Vijay Gangalam, Deepak Selvakumar, Reda Habak, Muslim Abdullah, Mohamed Ahmed Osama, Khlud Asanai, Noman Zafar, Sophia Lewis, Florence Kashora, Dixa Thakrar, Dean Rex, Annita Budzanowski, Jennifer Binnington, Simon Timbrell, Megan Ridgeway, Shirley Chan, Amani Asour, Adetayo Aderombi, Donald Menzies, Ali Murtada, Corina Dragu, Vincent Quan, Krashna Patel, Sesi Hotonu, Ashley Meikle, Ajay Belgaumkar, Prabhat Narayan, Thomas Badenoch, Frances Goulder, Katie Siggens, Kizzie Peters, Fiona Kirkham, Paul Froggatt, Karen Lai, Cristina Navarro, Dorinda Chandrabose, Simon Toh, Elizabeth Gemmill, Keira Lily, Mark Dilworth, Dimitrios Stamatiou, Alasdair Macmillan, Danielle Clyde, Majid Rashid, Gandrapu Srinivas, Katherine Buckley, Darren Smith, Henry Dowson, Gautam Singh, Seshu Kumar Bylapudi, Louise Phillips, Kimberley Hallam, Marisa Clemente, Karol Pal, George Ninkovic-Hall, Emila Paul, Theo Pelly, Joe Vance-Daniel, Venkatesh Kanakala, Edward J Nevins, James Dixon, Michael John, Jude Prince, Georgios Karagiannidis, Suzette Samlalsingh, Chrsitine Ozone, Amina Bouhelal, Siddhartha Handa, Sathasivam Rajeev, Ellen Ross, Ali Wadah, John Hallett, Shirish Tewari, Vinay Shah, Nick Reay-Jones, Salman Bodla, Harriet Corbett, Sumita Chhabra, Athanasios Tyraskis, Benjamin Allin, Angus Fitchie, Michael Stanton, Mark Vipond, Harry Dean, Matthew Boal, Jonathan Goring, Mahmoud Marei, Christian Verhoef, Jonathan Ducey, Chipo Mushonga, Dan Frith, Ashok Ram, Ferzine Mohamed, Nadine Dyar, Rick MacMahon, Mohammed Fakhrul-Aldeen, Iain Bain, Graham Branagan, Rachel Carten, Chee Wan Lai, Anindya Niyogi, Claudia Koh, Christian Fox, Stavros Loukogeorgakis, Joe Curry, Jayaram Sivaraj, Milda Jancauskaite, Helen Please, Wayne Fradley, Maki Jitsumara, Sinead Hassett, Ancuta Muntean, Sarah Yassin, Suzanne Lawther, Ciaran Durand, Mohamed Eltom, Kirsty Brennan, Clara Chong, Hasan Mukhtar, Hany Khalil, Stephanie Clark, Ashish Desai, Amulya Saxena, Joshua Cave, Alistair Sharples, Lukas O’Brien, George Kerans, Ashwini Ghorpade, Felicity Arthur, Muhammad Tobbal, Rachael Robertson, Ben Martin, Ben Woodward, Kieran McGovern, and Duncan Rutherford
Subjects: Pediatrics, RJ1-570
Abstract: Objectives Acute appendicitis is the most common surgical condition in children. In the UK, appendicectomy is the most common treatment with non-operative management unusual. Due to concerns about the risk of SARS-CoV-2 transmission during surgical procedures, surgeons were advised to consider non-operative treatment and avoid laparoscopy where possible. This study aims to report management and outcomes, to date, of children with appendicitis in the UK and Ireland during the COVID-19 pandemic.Design Survey of consultant surgeons who treat children with appendicitis that informed a prospective multicentre observational cohort study.Setting Data were collected from centres in the UK and Ireland for cases admitted between 1 April and 31 May 2020 (first 2 months of the COVID-19 pandemic) at both general surgical and specialist paediatric surgical centres.Participants The study cohort includes 838 children with a clinical and/or radiological diagnosis of acute appendicitis of which 527 (63%) were male.Main outcomes measured Primary outcome was treatment strategy used for acute appendicitis. Other outcomes reported include change in treatment strategy over time, use of diagnostic imaging and important patient outcomes to 30 days following hospital admission.Results From very early in the pandemic surgeons experienced a change in their management of children with appendicitis and almost all surgeons who responded to the survey anticipated further changes during the pandemic. Overall, 326/838 (39%) were initially treated non-operatively of whom 81/326 (25%) proceeded to appendicectomy within the initial hospital admission. Of cases treated initially surgically 243/512 (48%) were performed laparoscopically. Diagnostic imaging was used in 445/838 (53%) children. Cases treated non-operatively had a shorter hospital stay than those treated surgically but hospital readmissions within 30 days were similar between groups. In cases treated surgically the negative appendicectomy rate was 4.5%. There was a trend towards increased use of surgical treatment and from open to laparoscopic appendicectomy as the pandemic progressed.Conclusion Non-operative treatment of appendicitis has been widely used for the first time in children in the UK and Ireland and is safe and effective in selected patients. Overall patient outcomes do not appear to have been adversely impacted by change in management during the pandemic thus far.
Published: 2020
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47. Author Correction: Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Author: Adland, Emily, Millar, Jane, Bengu, Nomonde, Muenchhoff, Maximilian, Fillis, Rowena, Sprenger, Kenneth, Ntlantsana, Vuyokasi, Roider, Julia, Vieira, Vinicius, Govender, Katya, Adamson, John, Nxele, Nelisiwe, Ochsenbauer, Christina, Kappes, John, Mori, Luisa, van Lobenstein, Jeroen, Graza, Yeney, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Matthews, Philippa C., Poderos, Ruth Penya, Lluch, Marta Colomer, Puertas, Maria C., Prado, Julia G., McKerrow, Neil, Archary, Moherndran, Ndung’u, Thumbi, Groll, Andreas, Jooste, Pieter, Martinez-Picado, Javier, Altfeld, Marcus, and Goulder, Philip
Published: 2020
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48. Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection

Author: Adland, Emily, Millar, Jane, Bengu, Nomonde, Muenchhoff, Maximilian, Fillis, Rowena, Sprenger, Kenneth, Ntlantsana, Vuyokasi, Roider, Julia, Vieira, Vinicius, Govender, Katya, Adamson, John, Nxele, Nelisiwe, Ochsenbauer, Christina, Kappes, John, Mori, Luisa, van Lobenstein, Jeroen, Graza, Yeney, Chinniah, Kogielambal, Kapongo, Constant, Bhoola, Roopesh, Krishna, Malini, Matthews, Philippa C., Poderos, Ruth Penya, Lluch, Marta Colomer, Puertas, Maria C., Prado, Julia G., McKerrow, Neil, Archary, Moherndran, Ndung’u, Thumbi, Groll, Andreas, Jooste, Pieter, Martinez-Picado, Javier, Altfeld, Marcus, and Goulder, Philip
Published: 2020
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49. Conflicting Perceptions of the Status of Field Biology and Identification Skills in UK Education

Author: Goulder, Raymond and Scott, Graham W.
Abstract: Reviews of the state of biology fieldwork in UK schools and universities at the beginning of the twenty-first century (Barker, Slingsby, and Tilling 2002; Smith 2004) were not entirely pessimistic; rather they suggested ways forward that might lead to an increase in fieldwork. Whether their hopes have been realised has, perhaps, been revealed by later studies. In 2006, the National Foundation for Educational Research comprehensively surveyed the extent of learning outside the classroom in English schools (O'Donnell, Morris and Wilson 2006). This survey included all kinds of fieldwork as well as that in biology and it concluded that, although many commentators had argued that there was a decline in fieldwork, there was little evidence in support of decline. Schools and local authorities considered that provision had increased or remained largely the same over the previous five years. Field work by primary schools on school sites was commonly reported as increasing. Less encouraging, however, are the findings of a metastudy by Lock (2010) of publications between 1963 and 2009, although only three out of 13 of these reported surveys were done after 2000, which addressed biology fieldwork provision for 16-19 year olds in UK schools and colleges. This study suggested that according to several criteria (time in the field, the number of teachers taking fieldwork, teacher perception of change and the amount of residential fieldwork) the extent of fieldwork had declined. Other criteria (the number and type of habitats visited) showed no clear evidence of change. The current status of fieldwork in UK universities, not withstanding the negative comment that has been reported in this article, appears to be buoyant. Maw, Mauchline, and Park (2011) surveyed academics from 27 institutions by questionnaire in 2010 and found no evidence of a decrease in biological fieldwork over the previous five years. Furthermore, when staff from 27 universities were interviewed by Skype or telephone in 2012 (Mauchline, Peacock, and Park 2013) there was no evidence of decline in fieldwork over the previous five years; fieldwork was greatly valued and a future increase was predicted in some institutions. The funding of fieldwork in UK universities has been anomalous in that students have sometimes been charged for fieldwork costs whereas expensive consumables used in laboratory classes have been provided without extra charge. Mauchline, Peacock, and Park (2013) suggested that the introduction of full-cost fees from 2012 has led to the deletion of extra charges for fieldwork; they suggest that this may boost fieldwork. Other suggested positive factors are that the promise of fieldwork enhances student recruitment, that fieldwork skills enhance employability and that students enjoy doing fieldwork. This is supported by the authors'experience with students at Hull University; they found that students valued fieldwork because of its leading to outdoor career opportunities and students largely enjoyed the fieldwork experience (Goulder, Scott, and Scott 2013; Scott et al. 2012). Here the authors posit that all in all, although there is clearly much difference of opinion, they are unconvinced that biological fieldwork and identification skills are currently at significant risk in UK universities; they also believe that fieldwork in schools has the potential for a positive future.
Published: 2016
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50. Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection

Author: Draenert, Rika, Le Gall, Sylvie, Pfafferott, Katja J, Leslie, Alasdair J, Chetty, Polan, Brander, Christian, Holmes, Edward C, Chang, Shih-Chung, Feeney, Margaret E, Addo, Marylyn M, Ruiz, Lidia, Ramduth, Danni, Jeena, Prakash, Altfeld, Marcus, Thomas, Stephanie, Tang, Yanhua, Verrill, Cori L, Dixon, Catherine, Prado, Julia G, Kiepiela, Photini, Martinez-Picado, Javier, Walker, Bruce D, and Goulder, Philip JR
Subjects: Prevention, Genetics, Infectious Diseases, HIV/AIDS, Vaccine Related, Immunization, Vaccine Related (AIDS), Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Infection, Alleles, Amino Acid Sequence, Antigen Presentation, Base Sequence, Clone Cells, DNA, Viral, Epitopes, Gene Products, gag, Genetic Variation, HIV Antigens, HIV Infections, HIV-1, HLA-B Antigens, Humans, Molecular Sequence Data, Mutation, Sequence Homology, Amino Acid, T-Lymphocytes, Cytotoxic, Medical and Health Sciences, Immunology
Abstract: Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57+ HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57-restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus-infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-terminal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences.
Published: 2004

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