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1.
PLoS Pathog ; 17(7): e1009278, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34228762

RESUMO

Simian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with strain 68-1 Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work indicates that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in 68-1 RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that 68-1 RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including immune cell, toll-like receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly correlating with subsequent vaccine efficacy. Treatment of a separate RM cohort with IL-15 confirmed the central involvement of this cytokine in the protection signature, linking the major innate and adaptive immune gene expression networks that correlate with RhCMV/SIV vaccine efficacy. This change-from-baseline IL-15 response signature was also demonstrated to significantly correlate with vaccine efficacy in an independent validation cohort of vaccinated and challenged RMs. The differential IL-15 gene set response to vaccination strongly correlated with the pre-vaccination activity of this pathway, with reduced baseline expression of IL-15 response genes significantly correlating with higher vaccine-induced induction of IL-15 signaling and subsequent vaccine protection, suggesting that a robust de novo vaccine-induced IL-15 signaling response is needed to program vaccine efficacy. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that support the ability of vaccine-elicited unconventionally restricted CD8+ T cells to mediate protection against SIV challenge.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Interleucina-15/imunologia , Vacinas contra a SAIDS/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Citomegalovirus , Feminino , Vetores Genéticos , Macaca mulatta , Masculino , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle
2.
J Med Ethics ; 49(11): 776-778, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36878675

RESUMO

Sometimes researchers explicitly or implicitly conceive of authorship in terms of moral or ethical rights to authorship when they are dealing with authorship issues. Because treating authorship as a right can encourage unethical behaviours, such as honorary and ghost authorship, buying and selling authorship, and unfair treatment of researchers, we recommend that researchers not conceive of authorship in this way but view it as a description about contributions to research. However, we acknowledge that the arguments we have given for this position are largely speculative and that more empirical research is needed to better ascertain the benefits and risks of treating authorship on scientific publications as a right.

3.
Sci Eng Ethics ; 29(4): 22, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37341846

RESUMO

In health sciences, technical contributions may be undervalued and excluded in the author byline. In this paper, I demonstrate how authorship is a historical construct which perpetuates systemic injustices including technical undervaluation. I make use of Pierre Bourdieu's conceptual work to demonstrate how the power dynamics at play in academia make it very challenging to change the habitual state or "habitus". To counter this, I argue that we must reconceive technical contributions to not be a priori less important based on its nature when assigning roles and opportunities leading to authorship. I make this argument based on two premises. First, science has evolved due to major information and biotechnological innovation; this requires 'technicians' to acquire and exercise a commensurate high degree of both technical and intellectual expertise which in turn increases the value of their contribution. I will illustrate this by providing a brief historical view of work statisticians, computer programmers/data scientists and laboratory technicians. Second, excluding or undervaluing this type of work is contrary to norms of responsibility, fairness and trustworthiness of the individual researchers and of teams in science. Although such norms are continuously tested because of power dynamics, their importance is central to ethical authorship practice and research integrity. While it may be argued that detailed disclosure of contributions (known as contributorship) increases accountability by clearly identifying who did what in the publication, I contend that this may unintentionally legitimize undervaluation of technical roles and may decrease integrity of science. Finally, this paper offers recommendations to promote ethical inclusion of technical contributors.


Assuntos
Políticas Editoriais , Editoração , Humanos , Autoria , Responsabilidade Social , Pesquisadores
4.
Retrovirology ; 19(1): 15, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804422

RESUMO

BACKGROUND: Innate immunity and type 1 interferon (IFN) defenses are critical for early control of HIV infection within CD4 + T cells. Despite these defenses, some acutely infected cells silence viral transcription to become latently infected and form the HIV reservoir in vivo. Latently infected cells persist through antiretroviral therapy (ART) and are a major barrier to HIV cure. Here, we evaluated innate immunity and IFN responses in multiple T cell models of HIV latency, including established latent cell lines, Jurkat cells latently infected with a reporter virus, and a primary CD4 + T cell model of virologic suppression. RESULTS: We found that while latently infected T cell lines have functional RNA sensing and IFN signaling pathways, they fail to induce specific interferon-stimulated genes (ISGs) in response to innate immune activation or type 1 IFN treatment. Jurkat cells latently infected with a fluorescent reporter HIV similarly demonstrate attenuated responses to type 1 IFN. Using bulk and single-cell RNA sequencing we applied a functional genomics approach and define ISG expression dynamics in latent HIV infection, including HIV-infected ART-suppressed primary CD4 + T cells. CONCLUSIONS: Our observations indicate that HIV latency and viral suppression each link with cell-intrinsic defects in specific ISG induction. We identify a set of ISGs for consideration as latency restriction factors whose expression and function could possibly mitigate establishing latent HIV infection.


Assuntos
Infecções por HIV , Interferon Tipo I , Antivirais , Linfócitos T CD4-Positivos , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Latência Viral
5.
J Immunol ; 204(12): 3434-3444, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32376650

RESUMO

The diversity of Ig and TCR repertoires is a focal point of immunological studies. Rhesus macaques (Macaca mulatta) are key for modeling human immune responses, placing critical importance on the accurate annotation and quantification of their Ig and TCR repertoires. However, because of incomplete reference resources, the coverage and accuracy of the traditional targeted amplification strategies for profiling rhesus Ig and TCR repertoires are largely unknown. In this study, using long read sequencing, we sequenced four Indian-origin rhesus macaque tissues and obtained high-quality, full-length sequences for over 6000 unique Ig and TCR transcripts, without the need for sequence assembly. We constructed, to our knowledge, the first complete reference set for the constant regions of all known isotypes and chain types of rhesus Ig and TCR repertoires. We show that sequence diversity exists across the entire variable regions of rhesus Ig and TCR transcripts. Consequently, existing strategies using targeted amplification of rearranged variable regions comprised of V(D)J gene segments miss a significant fraction (27-53% and 42-49%) of rhesus Ig/TCR diversity. To overcome these limitations, we designed new rhesus-specific assays that remove the need for primers conventionally targeting variable regions and allow single cell level Ig and TCR repertoire analysis. Our improved approach will enable future studies to fully capture rhesus Ig and TCR repertoire diversity and is applicable for improving annotations in any model organism.


Assuntos
Imunoglobulinas/genética , Imunoglobulinas/imunologia , Macaca mulatta/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Transcriptoma/genética , Transcriptoma/imunologia , Animais , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Macaca mulatta/genética
6.
PLoS Pathog ; 15(4): e1007672, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30973942

RESUMO

Gastrointestinal (GI) mucosal dysfunction predicts and likely contributes to non-infectious comorbidities and mortality in HIV infection and persists despite antiretroviral therapy. However, the mechanisms underlying this dysfunction remain incompletely understood. Neutrophils are important for containment of pathogens but can also contribute to tissue damage due to their release of reactive oxygen species and other potentially harmful effector molecules. Here we used a flow cytometry approach to investigate increased neutrophil lifespan as a mechanism for GI neutrophil accumulation in chronic, treated HIV infection and a potential role for gastrointestinal dysbiosis. We report that increased neutrophil survival contributes to neutrophil accumulation in colorectal biopsy tissue, thus implicating neutrophil lifespan as a new therapeutic target for mucosal inflammation in HIV infection. Additionally, we characterized the intestinal microbiome of colorectal biopsies using 16S rRNA sequencing. We found that a reduced Lactobacillus: Prevotella ratio associated with neutrophil survival, suggesting that intestinal bacteria may contribute to GI neutrophil accumulation in treated HIV infection. Finally, we provide evidence that Lactobacillus species uniquely decrease neutrophil survival and neutrophil frequency in vitro, which could have important therapeutic implications for reducing neutrophil-driven inflammation in HIV and other chronic inflammatory conditions.


Assuntos
Colo/imunologia , Microbioma Gastrointestinal/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Reto/imunologia , Colo/microbiologia , Colo/patologia , Feminino , Infecções por HIV/virologia , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Reto/microbiologia , Reto/patologia
7.
J Hist Med Allied Sci ; 76(1): 53-77, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33211808

RESUMO

Efforts to improve the quality and quantity of seafarers in the Royal Navy and merchant service became a particular concern amidst the degeneration debates of late-Victorian Britain. Maritime reformers not only promoted fitness in adult sailors, but also particularly sought to improve health and physique of boy recruits in order to rear a new generation of healthy sailors. This article shows how both services experimented with tighter admission criteria and dietary and exercise reforms, and became early advocates of using metrical standards to exclude all but the fittest, healthiest boys from training opportunities. While the physical monitoring of boy recruits undoubtedly showed the value of early lifestyle interventions in fostering healthy development, the rising physical standards of British seafarers in this period was just as much the result of restrictive medical examinations as a commitment to welfare initiatives.


Assuntos
Militares/história , Medicina Naval/história , Adolescente , Criança , História do Século XIX , História do Século XX , Humanos , Masculino , Militares/estatística & dados numéricos , Reino Unido
8.
Lancet ; 393(10171): 550-559, 2019 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-30739690

RESUMO

BACKGROUND: Clinical and preclinical studies have shown that there are sex-based differences at the genetic, cellular, biochemical, and physiological levels. Despite this, numerous studies have shown poor levels of inclusion of female populations into medical research. These disparities in sex inclusion in research are further complicated by the absence of sufficient reporting and analysis by sex of study populations. Disparities in the inclusion of the sexes in medical research substantially reduce the utility of the results of such research for the entire population. The absence of sex-related reporting are problematical for the translation of research from the preclinical to clinical and applied health settings. Large-scale studies are needed to identify the extent of sex-related reporting and where disparities are more prevalent. In addition, while several studies have shown the dearth of female researchers in science, few have evaluated whether a scarcity of women in science might be related to disparities in sex inclusion and reporting. We aimed to do a cross-disciplinary analysis of the degree of sex-related reporting across the health sciences-from biomedical, to clinical, and public health research-and the role of author gender in sex-related reporting. METHODS: This bibliometric analysis analysed sex-related reporting in medical research examining more than 11·5 million papers indexed in Web of Science and PubMed between 1980 and 2016 and using sex-related Medical Subject Headings as a proxy for sex reporting. For papers that were published between 2008 and 2016 and could be matched with PubMed, we assigned a gender to first and last authors on the basis of their names, according to our gender assignment algorithm. We removed papers for which we could not determine the gender of either the first or last author. We grouped papers into three disciplinary categories (biomedical research, clinical medicine, and public health). We used descriptive statistics and regression analyses (controlling for the number of authors and representation of women in specific diseases, countries, continents, year, and specialty areas) to study associations between the gender of the authors and sex-related reporting. FINDINGS: Between Jan 1, 1980, and Dec 31, 2016, sex-related reporting increased from 59% to 67% in clinical medicine and from 36% to 69% in public health research. But for biomedical research, sex remains largely under-reported (31% in 2016). Papers with female first and last authors had an increased probability of reporting sex, with an odds ratio of 1·26 (95% CI 1·24 to 1·27), and sex-related reporting was associated with publications in journals with low journal impact factors. For publications in 2016, sex-related reporting of both male and female is associated with a reduction of -0·51 (95% CI -0·54 to -0·47) in journal impact factors. INTERPRETATION: Gender disparities in the scientific workforce and scarcity of policies on sex-related reporting at the journal and institutional level could inhibit effective research translation from bench to clinical studies. Diversification in the scientific workforce and in the research populations-from cell lines, to rodents, to humans-is essential to produce the most rigorous and effective medical research. FUNDING: Canada Research Chairs.


Assuntos
Autoria , Bibliometria , Pesquisa Biomédica , Medicina Clínica , Saúde Pública , Publicações/estatística & dados numéricos , Fatores Sexuais , Feminino , Humanos , Masculino
9.
Sci Eng Ethics ; 26(4): 1967-1993, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31161378

RESUMO

Scientific authorship serves to identify and acknowledge individuals who "contribute significantly" to published research. However, specific authorship norms and practices often differ within and across disciplines, labs, and cultures. As a consequence, authorship disagreements are commonplace in team research. This study aims to better understand the prevalence of authorship disagreements, those factors that may lead to disagreements, as well as the extent and nature of resulting misbehavior. Methods include an international online survey of researchers who had published from 2011 to 2015 (8364 respondents). Of the 6673 who completed the main questions pertaining to authorship disagreement and misbehavior, nearly half (46.6%) reported disagreements regarding authorship naming; and discipline, rank, and gender had significant effects on disagreement rates. Paradoxically, researchers in multidisciplinary teams that typically reflect a range of norms and values, were less likely to have faced disagreements regarding authorship. Respondents reported having witnessed a wide range of misbehavior including: instances of hostility (24.6%), undermining of a colleague's work during meetings/talks (16.4%), cutting corners on research (8.3%), sabotaging a colleague's research (6.4%), or producing fraudulent work to be more competitive (3.3%). These findings suggest that authorship disputes may contribute to an unhealthy competitive dynamic that can undermine researchers' wellbeing, team cohesion, and scientific integrity.


Assuntos
Autoria , Pesquisa Biomédica , Dissidências e Disputas , Má Conduta Científica , Feminino , Humanos , Masculino , Pesquisadores
10.
Sci Eng Ethics ; 26(4): 1995-2022, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31165383

RESUMO

Authorship is commonly used as the basis for the measurement of research productivity. It influences career progression and rewards, making it a valued commodity in a competitive scientific environment. To better understand authorship practices amongst collaborative teams, this study surveyed authors on collaborative journal articles published between 2011 and 2015. Of the 8364 respondents, 1408 responded to the final open-ended question, which solicited additional comments or remarks regarding the fair distribution of authorship in research teams. This paper presents the analysis of these comments, categorized into four main themes: (1) disagreements, (2) questionable behavior, (3) external influences regarding authorship, and (4) values promoted by researchers. Results suggest that some respondents find ways to effectively manage disagreements in a collegial fashion. Conversely, others explain how distribution of authorship can become a "blood sport" or a "horror story" which can negatively affect researchers' wellbeing, scientific productivity and integrity. Researchers fear authorship discussions and often try to avoid openly discussing the situation which can strain team interactions. Unethical conduct is more likely to result from deceit, favoritism, and questionable mentorship and may become more egregious when there is constant bullying and discrimination. Although values of collegiality, transparency and fairness were promoted by researchers, rank and need for success often overpowered ethical decision-making. This research provides new insight into contextual specificities related to fair authorship distribution that can be instrumental in developing applicable training tools to identify, prevent, and mitigate authorship disagreement.


Assuntos
Autoria , Pesquisa Biomédica , Pesquisadores , Feminino , Humanos , Masculino , Princípios Morais , Percepção , Publicações
11.
Biochemistry ; 57(7): 1063-1072, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29341605

RESUMO

The process of DNA replication is carried out with high efficiency and accuracy by DNA polymerases. The replicative polymerase in E. coli is DNA Pol III, which is a complex of 10 different subunits that coordinates simultaneous replication on the leading and lagging strands. The 1160-residue Pol III alpha subunit is responsible for the polymerase activity and copies DNA accurately, making one error per 105 nucleotide incorporations. The goal of this research is to determine the residues that contribute to the activity of the polymerase subunit. Homology modeling and the computational methods of THEMATICS and POOL were used to predict functionally important amino acid residues through their computed chemical properties. Site-directed mutagenesis and biochemical assays were used to validate these predictions. Primer extension, steady-state single-nucleotide incorporation kinetics, and thermal denaturation assays were performed to understand the contribution of these residues to the function of the polymerase. This work shows that the top 15 residues predicted by POOL, a set that includes the three previously known catalytic aspartate residues, seven remote residues, plus five previously unexplored first-layer residues, are important for function. Six previously unidentified residues, R362, D405, K553, Y686, E688, and H760, are each essential to Pol III activity; three additional residues, Y340, R390, and K758, play important roles in activity.


Assuntos
DNA Polimerase III/química , Escherichia coli/química , Domínio Catalítico , DNA Polimerase III/genética , DNA Polimerase III/metabolismo , Estabilidade Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Humanos , Mutagênese Sítio-Dirigida , Conformação Proteica
13.
Am J Bioeth ; 18(3): 29-41, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29466133

RESUMO

Various U.S. laws, such as the Clean Air Act and the Food Quality Protection Act, require additional protections for susceptible subpopulations who face greater environmental health risks. The main ethical rationale for providing these protections is to ensure that environmental health risks are distributed fairly. In this article, we (1) consider how several influential theories of justice deal with issues related to the distribution of environmental health risks; (2) show that these theories often fail to provide specific guidance concerning policy choices; and (3) argue that an approach to public decision making known as accountability for reasonableness can complement theories of justice in establishing acceptable environmental health risks for the general population and susceptible subpopulations. Since accountability for reasonableness focuses on the fairness of the decision-making process, not the outcome, it does not guarantee that susceptible subpopulations will receive a maximum level of protection, regardless of costs or other morally relevant considerations.


Assuntos
Exposição Ambiental/ética , Saúde Ambiental/ética , Alocação de Recursos/ética , Justiça Social/ética , Tomada de Decisões/ética , Exposição Ambiental/prevenção & controle , Política de Saúde , Humanos , Responsabilidade Social , Estados Unidos
14.
J Gen Virol ; 98(10): 2425-2437, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28884664

RESUMO

A few studies have highlighted the importance of the respiratory microbiome in modulating the frequency and outcome of viral respiratory infections. However, there are insufficient data on the use of microbial signatures as prognostic biomarkers to predict respiratory disease outcomes. In this study, we aimed to evaluate whether specific bacterial community compositions in the nasopharynx of children at the time of hospitalization are associated with different influenza clinical outcomes. We utilized retrospective nasopharyngeal (NP) samples (n=36) collected at the time of hospital arrival from children who were infected with influenza virus and had been symptomatic for less than 2 days. Based on their clinical course, children were classified into two groups: patients with mild influenza, and patients with severe respiratory or neurological complications. We implemented custom 16S rRNA gene sequencing, metagenomic sequencing and computational analysis workflows to classify the bacteria present in NP specimens at the species level. We found that increased bacterial diversity in the nasopharynx of children was strongly associated with influenza severity. In addition, patients with severe influenza had decreased relative abundance of Staphylococcus aureus and increased abundance of Prevotella (including P. melaninogenica), Streptobacillus, Porphyromonas, Granulicatella (including G. elegans), Veillonella (including V. dispar), Fusobacterium and Haemophilus in their nasopharynx. This pilot study provides proof-of-concept data for the use of microbial signatures as prognostic biomarkers of influenza outcomes. Further large prospective cohort studies are needed to refine and validate the performance of such microbial signatures in clinical settings.


Assuntos
Disbiose , Influenza Humana/complicações , Influenza Humana/diagnóstico , Microbiota , Nasofaringe/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Criança , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Humanos , Filogenia , Prognóstico , RNA Ribossômico 16S/genética , Estudos Retrospectivos , Análise de Sequência de DNA
15.
J Virol ; 90(10): 4981-4989, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26937040

RESUMO

UNLABELLED: An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4(+) T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies. IMPORTANCE: Due to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4(+) T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Vírus da Imunodeficiência Símia/imunologia , Animais , Antibacterianos/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Transplante de Microbiota Fecal/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Genes de RNAr , Infecções por HIV/imunologia , Infecções por HIV/microbiologia , Infecções por HIV/terapia , Infecções por HIV/virologia , Humanos , Intestinos/citologia , Intestinos/imunologia , Intestinos/microbiologia , Ativação Linfocitária/efeitos dos fármacos , Macaca mulatta , Projetos Piloto , RNA Ribossômico 16S/genética , Síndrome de Imunodeficiência Adquirida dos Símios/microbiologia , Vírus da Imunodeficiência Símia/genética , Células Th17/imunologia , Carga Viral/efeitos dos fármacos
16.
Kennedy Inst Ethics J ; 27(3): 371-411, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28989166

RESUMO

In academia, authorship on publications confers merit as well as responsibility. The respective disciplines adhere to their "typical" authorship practices: individuals may be named in alphabetical order (e.g., in economics, mathematics), ranked in decreasing level of contribution (e.g., biomedical sciences), or the leadership role may be listed last (e.g., laboratory sciences). However, there is no specific, generally accepted guidance regarding authorship distribution in multidisciplinary teams, something that can lead to significant tensions and even conflict. Using Scanlon's contractualism as a basis, I propose a conceptual foundation for the ethical distribution of authorship in multidisciplinary teams; it features four relevant principles: desert, just recognition, transparency, and collegiality. These principles can serve in the development of a practical framework to support ethical and nonarbitrary authorship distribution, which hopefully would help reduce confusion and conflict, promote agreement, and contribute to synergy in multidisciplinary collaborative research.


Assuntos
Autoria , Teoria Ética , Comunicação Interdisciplinar , Pesquisa Biomédica , Relações Interprofissionais , Revelação da Verdade
17.
Health Res Policy Syst ; 15(1): 73, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28851401

RESUMO

BACKGROUND: In 1982, the Annals of Virology published a paper showing how Liberia has a highly endemic potential of Ebola warning health authorities of the risk for potential outbreaks; this journal is only available by subscription. Limiting the accessibility of such knowledge may have reduced information propagation toward public health actors who were indeed surprised by and unprepared for the 2014 epidemic. Open access (OA) publication can allow for increased access to global health research (GHR). Our study aims to assess the use, cost and impact of OA diffusion in the context of GHR. METHOD: A total of 3366 research articles indexed under the Medical Heading Subject Heading "Global Health" published between 2010 and 2014 were retrieved using PubMed to (1) quantify the uptake of various types of OA, (2) estimate the article processing charges (APCs) of OA, and (3) analyse the relationship between different types of OA, their scholarly impact and gross national income per capita of citing countries. RESULTS: Most GHR publications are not available directly on the journal's website (69%). Further, 60.8% of researchers do not self-archive their work even when it is free and in keeping with journal policy. The total amount paid for APCs was estimated at US$1.7 million for 627 papers, with authors paying on average US$2732 per publication; 94% of APCs were paid to journals owned by the ten most prominent publication houses from high-income countries. Researchers from low- and middle-income countries are generally citing less expensive types of OA, while researchers in high-income countries are citing the most expensive OA. CONCLUSIONS: Although OA may help in building global research capacity in GHR, the majority of publications remain subscription only. It is logical and cost-efficient for institutions and researchers to promote OA by self-archiving publications of restricted access, as it not only allows research to be cited by a broader audience, it also augments citation rates. Although OA does not ensure full knowledge transfer from research to practice, limiting public access can negatively impact implementation and outcomes of health policy and reduce public understanding of health issues.


Assuntos
Acesso à Informação , Pesquisa Biomédica/economia , Saúde Global , Publicação de Acesso Aberto/economia , Humanos , Conhecimento , Publicações Periódicas como Assunto , Publicações
18.
Foodborne Pathog Dis ; 14(9): 494-501, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28692343

RESUMO

Clostridium botulinum strains are prevalent in the environment and produce a potent neurotoxin that causes botulism, a rare but serious paralytic disease. In 2010, a national PulseNet database was established to curate C. botulinum pulsotypes and facilitate epidemiological investigations, particularly for serotypes A and B strains frequently associated with botulism cases in the United States. Between 2010 and 2014 we performed pulsed-field gel electrophoresis (PFGE) using a PulseNet protocol, uploaded the resulting PFGE patterns into a national database, and analyzed data according to PulseNet criteria (UPGMA clustering, Dice coefficient, 1.5% position tolerance, and 1.5% optimization). A retrospective data analysis was undertaken on 349 entries comprised of type A and B strains isolated from foodborne and infant cases to determine epidemiological relevance, resolution of the method, and the diversity of the database. Most studies to date on the pulsotype diversity of C. botulinum have encompassed very small sets of isolates; this study, with over 300 isolates, is more comprehensive than any published to date. Epidemiologically linked isolates had indistinguishable patterns, except in four instances and there were no obvious geographic trends noted. Simpson's Index of Diversity (D) has historically been used to demonstrate species diversity and abundance within a group, and is considered a standard descriptor for PFGE databases. Simpson's Index was calculated for each restriction endonuclease (SmaI, XhoI), the pattern combination SmaI-XhoI, as well as for each toxin serotype. The D values indicate that both enzymes provided better resolution for serotype B isolates than serotype A. XhoI as the secondary enzyme provided little additional discrimination for C. botulinum. SmaI patterns can be used to exclude unrelated isolates during a foodborne outbreak, but pulsotypes should always be considered concurrently with available epidemiological data.


Assuntos
Botulismo/microbiologia , Clostridium botulinum/classificação , Clostridium botulinum/genética , Eletroforese em Gel de Campo Pulsado/métodos , Doenças Transmitidas por Alimentos/microbiologia , Técnicas de Tipagem Bacteriana , Biodiversidade , Botulismo/epidemiologia , Clostridium botulinum/imunologia , Monitoramento Epidemiológico , Doenças Transmitidas por Alimentos/epidemiologia , Humanos , Lactente , Estudos Retrospectivos , Sorogrupo , Estados Unidos/epidemiologia
20.
BMC Med Ethics ; 15: 42, 2014 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-24885855

RESUMO

BACKGROUND: Over the past two decades, the promotion of collaborative partnerships involving researchers from low and middle income countries with those from high income countries has been a major development in global health research. Ideally, these partnerships would lead to more equitable collaboration including the sharing of research responsibilities and rewards. While collaborative partnership initiatives have shown promise and attracted growing interest, there has been little scholarly debate regarding the fair distribution of authorship credit within these partnerships. DISCUSSION: In this paper, we identify four key authorship issues relevant to global health research and discuss their ethical and practical implications. First, we argue that authorship guidance may not adequately apply to global health research because it requires authors to write or substantially revise the manuscript. Since most journals of international reputation in global health are written in English, this would systematically and unjustly exclude non-English speaking researchers even if they have substantially contributed to the research project. Second, current guidance on authorship order does not address or mitigate unfair practices which can occur in global health research due to power differences between researchers from high and low-middle income countries. It also provides insufficient recognition of "technical tasks" such as local participant recruitment. Third, we consider the potential for real or perceived editorial bias in medical science journals in favour of prominent western researchers, and the risk of promoting misplaced credit and/or prestige authorship. Finally, we explore how diverse cultural practices and expectations regarding authorship may create conflict between researchers from low-middle and high income countries and contribute to unethical authorship practices. To effectively deal with these issues, we suggest: 1) undertaking further empirical and conceptual research regarding authorship in global health research; 2) raising awareness on authorship issues in global health research; and 3) developing specific standards of practice that reflect relevant considerations of authorship in global health research. SUMMARY: Through review of the bioethics and global health literatures, and examination of guidance documents on ethical authorship, we identified a set of issues regarding authorship in collaborative partnerships between researchers from low-middle income countries and high income countries. We propose several recommendations to address these concerns.


Assuntos
Autoria , Comportamento Cooperativo , Países Desenvolvidos , Países em Desenvolvimento , Pesquisa sobre Serviços de Saúde/ética , Editoração/ética , Pesquisadores/ética , Bioética , Políticas Editoriais , Feminino , Saúde Global , Guias como Assunto , Humanos , Masculino , Publicações Periódicas como Assunto , Responsabilidade Social
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