scholarly journals Temporal Evolution of the Resistance Genotypes of Plasmodium Falciparum in Isolates From Equatorial Guinea During 20 Years (1999 to 2019).

2021 ◽  
Author(s):  
Pedro Berzosa ◽  
Irene Molina-de la Fuente ◽  
Thuy-Huong Ta-Tang ◽  
Vicenta González ◽  
Luz García ◽  
...  
Keyword(s):  
Nested Pcr ◽  
Gene Mutations ◽  
Equatorial Guinea ◽  
Upward Trend ◽  
Synonymous Mutations ◽  
Treatment Changes ◽  
Resistance Markers ◽  
Parasite Populations ◽  
Over Time ◽  
Made In

Abstract Background: Malaria is one of the deadliest disease in the world, particularly in Africa. The resistance to antimalarial drugs is one of the most important problems to global malaria control. The study assess the evolution of the different resistance markers over time and the possible influence of the interventions and treatment changes that have been made in Equatorial Guinea.Methods: 1223 biological samples distributed from 1999 to 2019 were included in the study. The screening of the mutations in pfdhfr, pfdhps, pfmdr1 and pfcrt genes were carried out by nested PCR and RFLPs, and the study of pfk13 genes was carried out by nested PCR, followed by sequencing to determine the presence of mutations Results: the haplotypes partially and fully resistant (pfdhfr + pfdhps) increase over time. In 2019, the fully resistant is increasing although super resistant remains lower. There is also a continued decline over time in pfmdr1 and pfcrt gene mutations. Since 2008, when ACTs were introduced in the country, the number of mutations detected in pfk13 has been increasing over time, with more mutations being observed in 2019. In this year, were detected 2 synonymous and 5 non-synonymous mutations, although are not related to resistance to ACTs. In addition, the non-synonymous A578S mutation, the most frequent on the African continent, was detected in 2013, although it has not been detected in the following years.Conclusions: The withdrawal of the use of CQ as a treatment in the country has been effective over time, as wild-type parasite populations outnumber mutant populations. The upward trend observed in SP resistance markers evidence its misuse alone or in combination with AS or AQ in some areas of the country, this allows selective pressure from SP to continue. SNPs 540E and 581G do not exceed the limit of 50% and 10% respectively, which means that SP as an IPT is still effective in the country. As for the pfk13 gene, no mutations have been detected in relation to resistance to ACTs. However, in 2019 there is a greater accumulation of non-synonymous mutations compared to years prior to 2008.

scholarly journals Temporal evolution of the resistance genotypes of Plasmodium falciparum in isolates from Equatorial Guinea during 20 years (1999 to 2019)

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Pedro Berzosa ◽  
Irene Molina de la Fuente ◽  
Thuy-Huong Ta-Tang ◽  
Vicenta González ◽  
Luz García ◽  
...  
Keyword(s):  
Nested Pcr ◽  
Intermittent Preventive Treatment ◽  
Gene Mutations ◽  
Preventive Treatment ◽  
Equatorial Guinea ◽  
Nucleotide Polymorphisms ◽  
Synonymous Mutations ◽  
Length Polymorphisms ◽  
Resistance Markers ◽  
Over Time

Abstract Background Malaria is one of the deadliest diseases in the world, particularly in Africa. As such, resistance to anti-malarial drugs is one of the most important problems in terms of global malaria control. This study assesses the evolution of the different resistance markers over time and the possible influence of interventions and treatment changes that have been made in Equatorial Guinea. Methods A total of 1223 biological samples obtained in the period 1999 to 2019 were included in the study. Screening for mutations in the pfdhfr, pfdhps, pfmdr1, and pfcrt genes was carried out by nested PCR and restriction-fragment length polymorphisms (RFLPs), and the study of pfk13 genes was carried out by nested PCR, followed by sequencing to determine the presence of mutations. Results The partially and fully resistant haplotypes (pfdhfr + pfdhps) were found to increase over time. Moreover, in 2019, the fully resistant haplotype was found to be increasing, although its super-resistant counterpart remains much less prevalent. A continued decline in pfmdr1 and pfcrt gene mutations over time was also found. The number of mutations detected in pfk13 has increased since 2008, when artemisinin-based combination therapy (ACT) were first introduced, with more mutations being observed in 2019, with two synonymous and five non-synonymous mutations being detected, although these are not related to resistance to ACT. In addition, the non-synonymous A578S mutation, which is the most frequent on the African continent, was detected in 2013, although not in the following years. Conclusions Withdrawal of the use of chloroquine (CQ) as a treatment in Equatorial Guinea has been shown to be effective over time, as wild-type parasite populations outnumber mutant populations. The upward trend observed in sulfadoxine-pyrimethamine (SP) resistance markers suggest its misuse, either alone or in combination with artesunate (AS) or amodiaquine (AQ), in some areas of the country, as was found in a previous study conducted by this group, which allows selective pressure from SP to continue. Single nucleotide polymorphisms (SNPs) 540E and 581G do not exceed the limit of 50 and 10%, respectively, thus meaning that SP is still effective as an intermittent preventive treatment (IPT) in this country. As for the pfk13 gene, no mutations have been detected in relation to resistance to ACT. However, in 2019 there is a greater accumulation of non-synonymous mutations compared to years prior to 2008. Graphical Abstract

A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Varvara Kanti ◽  
Lia Puder ◽  
Irina Jahnke ◽  
Philipp Maximilian Krabusch ◽  
Jan Kottner ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Skin Pigmentation ◽  
Gene Mutations ◽  
Continuous Treatment ◽  
Whole Body ◽  
Hair Color ◽  
Phase 2 ◽  
Loss Of Function ◽  
The Impact ◽  
Over Time

<b><i>Background and Objectives:</i></b> Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist <i>setmelanotide</i> in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with <i>setmelanotide,</i> changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R). Here, we describe in detail the findings of dermatological examinations and measurements of skin pigmentation during this treatment over time and discuss the impact of these changes on patient safety. <b><i>Methods:</i></b> In an investigator-initiated, phase 2, open-label pilot study, 2 patients with loss-of-function POMC gene mutations and 3 patients with loss-of-function variants in LEPR were treated with the MC4R agonist <i>setmelanotide</i>. Dermatological examination, dermoscopy, whole body photographic documentation, and spectrophotometric measurements were performed at screening visit and approximately every 3 months during the course of the study. <b><i>Results:</i></b> We report the results of a maximum treatment duration of 46 months. Skin pigmentation increased in all treated patients, as confirmed by spectrophotometry. During continuous treatment, the current results indicate that elevated tanning intensity levels may stabilize over time. Lips and nevi also darkened. In red-haired study participants, hair color changed to brown after initiation of <i>setmelanotide</i> treatment. <b><i>Discussion:</i></b> <i>Setmelanotide</i> treatment leads to skin tanning and occasionally hair color darkening in both POMC- and LEPR-deficient patients. No malignant skin changes were observed in the patients of this study. However, the results highlight the importance of regular skin examinations before and during MC4R agonist treatment.

Quel corpus pour l’étude du dialecte niçois ?

2021 ◽  
Vol 137 (2) ◽  
pp. 344-361
Author(s):  
Philippe Del Giudice
Keyword(s):  
Middle Ages ◽  
Written Language ◽  
Linguistic Features ◽  
Descriptive Grammar ◽  
Written Production ◽  
Starting Point ◽  
Social Use ◽  
Over Time ◽  
Made In ◽  
Do So

Abstract A new project has just been launched to write a synchronic, descriptive grammar of Niçois, the Occitan dialect of Nice. In this article, I define the corpus of the research. To do so, I first review written production from the Middle Ages to the present. I then analyze the linguistic features of Niçois over time, in order to determine the precise starting point of the current language state. But because of reinforced normativism and the decreasing social use of Niçois among the educated population, written language after WWII became artificial and does not really correspond to recordings made in the field. The corpus will thus be composed of writings from the 1820’s to WWII and recordings from the last few decades.

scholarly journals Molecular Basis of In Vivo Resistance to Sulfadoxine-Pyrimethamine in African Adult Patients Infected withPlasmodium falciparum Malaria Parasites

1998 ◽  
Vol 42 (7) ◽  
pp. 1811-1814 ◽  
Author(s):  
Leonardo K. Basco ◽  
Rachida Tahar ◽  
Pascal Ringwald
Keyword(s):  
Dihydrofolate Reductase ◽  
Point Mutations ◽  
Gene Mutations ◽  
Adult Patients ◽  
Wild Type ◽  
Dihydropteroate Synthase ◽  
Reductase Gene ◽  
Parasite Populations

ABSTRACT In vitro sulfadoxine and pyrimethamine resistance has been associated with point mutations in the dihydropteroate synthase and dihydrofolate reductase domains, respectively, but the in vivo relevance of these point mutations has not been well established. To analyze the correlation between genotype and phenotype, 10 Cameroonian adult patients were treated with sulfadoxine-pyrimethamine and followed up for 28 days. After losses to follow-up (n = 1) or elimination of DNA samples due to mixed parasite populations with pyrimethamine-sensitive and pyrimethamine-resistant profiles (n = 3), parasite genomic DNA from day 0 blood samples of six patients were analyzed by DNA sequencing. Three patients who were cured had isolates characterized by a wild-type or mutant dihydrofolate reductase gene (with one or two mutations) and a wild-type dihydropteroate synthase gene. Three other patients who failed to respond to sulfadoxine-pyrimethamine treatment carried isolates with triple dihydrofolate reductase gene mutations and either a wild-type or a mutant dihydropteroate synthase gene. Three dihydrofolate reductase gene codons (51, 59, and 108) may be reliable genetic markers that can accurately predict the clinical outcome of sulfadoxine-pyrimethamine treatment in Africa.

Lessons learned in intellectual capital management in Germany between 2000 and 2020 – History, applications, outlook

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Manfred Bornemann ◽  
Kay Alwert ◽  
Markus Will
Keyword(s):  
Development Strategy ◽  
Intellectual Capital ◽  
Business Models ◽  
Business Processes ◽  
Lessons Learned ◽  
Strategy Development ◽  
Management Approach ◽  
Content Type ◽  
Over Time ◽  
Made In

PurposeThis article reports on the background, the conceptual ideas and the lessons learned from over more than 20 years of IC Statements and Management with a country focus on Germany and some international developments. It calls for an integrated management approach for IC and offers case study evidence on how to accomplish this quest.Design/methodology/approachReport on the German initiative “Intellectual Capital Statement made in Germany” (ICS m.i.G.). A brief review of the literature describes the background and theoretical foundation of the German IC method. A short description of the method is followed by four detailed case studies to illustrate long-term impact of IC management in very different organizations. A discussion of Lessons Learned from more than 200 implementations and an outlook on current and future developments finalizes the article.FindingsIC Statements made in Germany (ICS m.i.G.) was successful in providing a framework to systematically identify IC, evaluate the status quo of IC relative to the strategic requirements, visualize interdependencies of IC, business processes and business results as well as to connect IC reporting with internal management routines and external communication. However, ICS is not an insulated method but delivers the maximum benefit when integrated with strategy development, strategy implementation, business process optimization accompanied by change management routines. Strong ties to human resource management, information technology departments, quality management, research and development teams as well as business operations as the core of an organization help to yield the most for ICS m.i.G. Over time, the focus of managing IC changes and maturity leads to deutero learning.Practical implicationsICS m.i.G. proved easy to apply, cost efficient for SMEs, larger corporations and networks. It helps to better accomplish their objectives and to adjust their business models. The guidelines in German and English as well as a software application released were downloaded more than 100,000 times. A certification process based on a three-tier training module is available and was successfully completed by more than 400 practitioners. ICS m.i.G. is supporting current standards of knowledge management, such as ISO 9001, ISO 30401 or DIN SPEC PAS 91443 and therefore will most likely have a continuing impact on knowledge-based value creation.Originality/valueThis paper reports lessons learned from the country-wide IC initiative in Germany over the last 20 years initiated and supported by the authors. Several elements of the method have been published over time, but so far no comprehensive view on Lessons Learned had been published.

Qualitative longitudinal research: researching fatherhood and fathers’ experiences

2018 ◽  
Author(s):  
Tina Miller
Keyword(s):  
Longitudinal Study ◽  
Qualitative Study ◽  
Research Design ◽  
Longitudinal Research ◽  
Methodological Issues ◽  
Research Project ◽  
Transition To Motherhood ◽  
Transition To Fatherhood ◽  
Over Time ◽  
Made In

This chapter focuses on a qualitative longitudinal (QL) research project, Transition to Fatherhood, and later episodes of fathering and fatherhood experiences. It begins by exploring the research design of this study and considers the inherent gendered and other assumptions made in it, which mirrors an earlier research project on Transition to Motherhood. Following an examination of some of the methodological issues that arose during this qualitative longitudinal study, the chapter turns to reflect on the important question of what adding time into a qualitative study can do. It considers what happens when narratives collected in later interviews are incorporated into earlier analysis and findings as lives and fatherhood experiences change, as well as the benefits of researching individuals over time.

scholarly journals Personal Identity: The Simple and Complex Views Revisited

Disputatio ◽  
2019 ◽  
Vol 11 (52) ◽  
pp. 9-22
Author(s):  
Harold Noonan
Keyword(s):  
Personal Identity ◽  
Clear Sense ◽  
Reasonable Possibility ◽  
Time Fall ◽  
Recent Account ◽  
Over Time ◽  
Made In ◽  
The Way

Abstract Eric Olson has argued, startlingly, that no coherent account can be giv- en of the distinction made in the personal identity literature between ‘complex views’ and ‘simple views’. ‘We tell our students,’ he writes, ‘that accounts of personal identity over time fall into [these] two broad categories’. But ‘it is impossible to characterize this distinction in any satisfactory way. The debate has been systematically misdescribed’. I argue, first, that, for all Olson has said, a recent account by Noonan provides the coherent characterization he claims impossible. If so we have not been wrong all along in the way he says in what we have been telling our students. I then give an account of the distinction between the reductionist and non-reductionist positions which makes it differ- ent from the complex/simple distinction. The aim is to make clear sense of the notion of a not simple but non-reductionist position — which seems an eminently reasonable possibility and something it may also be useful to tell our students about.

A Review of Measurement Equivalence in Organizational Research: What's Old, What's New, What's Next?

2021 ◽  
pp. 109442812110565
Author(s):  
Ajay V. Somaraju ◽  
Christopher D. Nye ◽  
Jeffrey Olenick
Keyword(s):  
Review Paper ◽  
Measurement Equivalence ◽  
Future Directions ◽  
Organizational Research ◽  
Potential Sources ◽  
Organizational Constructs ◽  
Organizational Literature ◽  
Over Time ◽  
Made In ◽  
Highly Cited

The study of measurement equivalence has important implications for organizational research. Nonequivalence across groups or over time can affect the results of a study and the conclusions that are drawn from it. As a result, the review paper by Vandenberg & Lance (2000) has been highly cited and has played an important role in understanding the measurement of organizational constructs. However, that paper is now 20 years old, and a number of advances have been made in the application and interpretation of measurement equivalence (ME) since its publication. Therefore, the goal of the present paper is to provide an updated review of ME techniques that describes recent advances in testing for ME and proposes a taxonomy of potential sources of nonequivalence. Finally, we articulate recommendations for applying these newer methods and consider future directions for measurement equivalence research in the organizational literature.

Introduction

2019 ◽  
pp. 1-26
Author(s):  
Sean Akerman
Keyword(s):  
Narrative Approaches ◽  
History Of ◽  
Over Time ◽  
Made In ◽  
Tibetan Exile

This chapter introduces the author’s fieldwork and the focus of the book: using narrative approaches to understand and represent exile. The chapter reviews the progress narrative work has made in the discipline of psychology and how it provides a useful approach to the study of exile for reasons that are theoretical, methodological, and rhetorical. The author sketches the history of the Tibetan exile and explains how it provides a useful site to investigate the issues that are at the heart of the book, including the transmission of stories, and traumas, over time. Finally, the author introduces the informants who feature significantly in the book.

Color and Status of Slaves

2017 ◽  
Author(s):  
Paul Schor
Keyword(s):  
Legal Status ◽  
Black Blood ◽  
Antebellum Era ◽  
White Person ◽  
Definition Of ◽  
Over Time ◽  
Made In

This chapter discusses how the definition of race varied over time and place and remained uncertain in cases judged by the courts in the antebellum era. In the 1850s, a claim of whiteness was an argument that could be made in court to obtain liberty, since a white person could not be a slave. Legal status did not rest on the same forms of proof as the census, but the two perspectives overlapped. Comparing the procedures for determining the legal status of slaves with the procedure adopted by the census for assigning the color of individuals shows the profound ambiguity of the latter. The language used by the legislators in 1850 and retained until the end of the century was clearly that of the scientific rules then in favor, based on the parts of black blood and of genealogy. However, in practice individuals were judged by their appearance rather than genealogy.

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