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Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides. Global syphilis prevalence has been increasing. Sequencing and analysis of a global collection of 726 Treponema pallidum samples reveal globally circulating lineages linked t

Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides., Funding agencies:National Health and Medical Research Council of Australia 1174555 United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) R01 AI123196 UK Research & Innovation (UKRI)Medical Research Council UK (MRC) MR/V027956/1 United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA R01 AI42143DH | NIHR | Programme Development Grants (NIHR Programme Development Grants) NIHR200125 European and Developing Countries Clinical Trials Partnership (EDCTP) RIA2018D-249

Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per mu L). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virolog

Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per mu L). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virolog

Objectives: The aim of this study was to characterize the prevalence and patterns of genotypic integrase inhibitor (INI) resistance in relation to HIV-1 clade. Methods: The cohort comprised 533 INI-naive subjects and 255 raltegravir recipients with viraemia who underwent integrase sequencing in routine care across Europe, including 134/533 (25.1%) and 46/255 (18.0%), respectively, with non-B clades (A, C, D, F, G, CRF01, CRF02, other CRFs, complex). Results: No major INI resistance-associated mutations (RAMs) occurred in INI-naive subjects. Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K+G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%). In addition, four (1.6%) raltegravir recipients showed novel mutations at recognized resistance sites (E92A, S147I, N155D, N155Q) and novel mutations at other integrase positions that were statistically associated with raltegravir exposure (K159Q/R, I161L/M/T/V, E170A/G). Comparing subtype B with non-B clades, Q148H/R/K occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005). Intermediate-to high-level cross-resistance to twice-daily dolutegravirwas predicted in 40/255 (15.7%) subjects, more commonly in subtype B versus non-B clades (39/209, 18.7% versus 1/46, 2.2%; P = 0.003). A glycine (G) to serine (S) substitution at integrase position 140 required one nucleotide change in subtype B and two nucleotide changes in all non-B clades. Conclusions: No major INI resistance mutations occurred in INI-naive subjects. Reduced occurrence of Q148H/R/K+ G140S/A was seen in non-B clades versus subtype B, and was explained by the higher genetic barrier to the G140S mutation observed in all non-B clades analysed.

Objectives: The aim of this study was to characterize the prevalence and patterns of genotypic integrase inhibitor (INI) resistance in relation to HIV-1 clade. Methods: The cohort comprised 533 INI-naive subjects and 255 raltegravir recipients with viraemia who underwent integrase sequencing in routine care across Europe, including 134/533 (25.1%) and 46/255 (18.0%), respectively, with non-B clades (A, C, D, F, G, CRF01, CRF02, other CRFs, complex). Results: No major INI resistance-associated mutations (RAMs) occurred in INI-naive subjects. Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K+G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%). In addition, four (1.6%) raltegravir recipients showed novel mutations at recognized resistance sites (E92A, S147I, N155D, N155Q) and novel mutations at other integrase positions that were statistically associated with raltegravir exposure (K159Q/R, I161L/M/T/V, E170A/G). Comparing subtype B with non-B clades, Q148H/R/K occurred in 42/209 (20.1%) versus 2/46 (4.3%) subjects (P = 0.009) and G140S/A occurred in 36/209 (17.2%) versus 1/46 (2.2%) subjects (P = 0.005). Intermediate-to high-level cross-resistance to twice-daily dolutegravirwas predicted in 40/255 (15.7%) subjects, more commonly in subtype B versus non-B clades (39/209, 18.7% versus 1/46, 2.2%; P = 0.003). A glycine (G) to serine (S) substitution at integrase position 140 required one nucleotide change in subtype B and two nucleotide changes in all non-B clades. Conclusions: No major INI resistance mutations occurred in INI-naive subjects. Reduced occurrence of Q148H/R/K+ G140S/A was seen in non-B clades versus subtype B, and was explained by the higher genetic barrier to the G140S mutation observed in all non-B clades analysed.

Tjaart van der Walt: slave of Christ – δοῦλος Χριστοῦ Tjaart van der Walt has carried an array of titles: from Boy, to Young Man, to Mister, to Reverend, to Doctorandus, to Doctor, to Professor, to Rector, to Vice-Chancellor, to CEO, to Ambassador! But the one title he gladly accepts, is “slave of Christ” – or in the Greek he loves so much: δοῦλος Χριστοῦ (doulos Christou)! This has become typical of him and his life: a slave taking his instructions from Jesus Christ as his Owner, his Κύριος (Kurios), being willing to – in each situation and in relationship with any person or organisation – put on his slave clothing, roll up his sleeves, and serve! In this narrative of the life of Tjaart van der Walt we do not want to share lists of successes and failures, but rather we survey the serving life of this “slave of Christ”, as if from an Archimedes vantage point. The present, November 2011, is this Archimedes vantage point., Tjaart van der Walt: slaaf van Christus – δοῦλος Χριστοῦ Tjaart van der Walt het in sy lewe baie titels gedra: van Boetman, tot Jongman, tot Meneer, tot Dominee, tot Doctorandus, tot Doktor, tot Professor, tot Rektor, tot Visekansellier, tot Hoof Uitvoerende Beampte, tot Ambassadeur! Maar die één titel wat hy met graagte dra, is “slaaf van Christus” – of in sy geliefde Grieks: δοῦλος Χριστοῦ (doulos Christou)! Dít is wat sy lewe kenmerk: ’n slaaf wat onder opdrag van die Here Jesus Christus as sy Eienaar, sy Κύριος (Kurios), bereid is om in elke situasie en in verhouding met watter mens of organisasie ook al, die slaafklere aan te trek, die moue op te rol, en te díén! In hierdie narratief van die lewe van Tjaart van der Walt wil ons nie lysies maak van prestasies en mislukkings, van hoogte- en laagtepunte nie, maar eerder die dienpad van hierdie “slaaf van Christus” in oënskou neem, asof van ’n archimedespunt af. Die hede, November 2011, is hierdie archimedespunt.

Tjaart van der Walt: slave of Christ – δοῦλος Χριστοῦ Tjaart van der Walt has carried an array of titles: from Boy, to Young Man, to Mister, to Reverend, to Doctorandus, to Doctor, to Professor, to Rector, to Vice-Chancellor, to CEO, to Ambassador! But the one title he gladly accepts, is “slave of Christ” – or in the Greek he loves so much: δοῦλος Χριστοῦ (doulos Christou)! This has become typical of him and his life: a slave taking his instructions from Jesus Christ as his Owner, his Κύριος (Kurios), being willing to – in each situation and in relationship with any person or organisation – put on his slave clothing, roll up his sleeves, and serve! In this narrative of the life of Tjaart van der Walt we do not want to share lists of successes and failures, but rather we survey the serving life of this “slave of Christ”, as if from an Archimedes vantage point. The present, November 2011, is this Archimedes vantage point., Tjaart van der Walt: slaaf van Christus – δοῦλος Χριστοῦ Tjaart van der Walt het in sy lewe baie titels gedra: van Boetman, tot Jongman, tot Meneer, tot Dominee, tot Doctorandus, tot Doktor, tot Professor, tot Rektor, tot Visekansellier, tot Hoof Uitvoerende Beampte, tot Ambassadeur! Maar die één titel wat hy met graagte dra, is “slaaf van Christus” – of in sy geliefde Grieks: δοῦλος Χριστοῦ (doulos Christou)! Dít is wat sy lewe kenmerk: ’n slaaf wat onder opdrag van die Here Jesus Christus as sy Eienaar, sy Κύριος (Kurios), bereid is om in elke situasie en in verhouding met watter mens of organisasie ook al, die slaafklere aan te trek, die moue op te rol, en te díén! In hierdie narratief van die lewe van Tjaart van der Walt wil ons nie lysies maak van prestasies en mislukkings, van hoogte- en laagtepunte nie, maar eerder die dienpad van hierdie “slaaf van Christus” in oënskou neem, asof van ’n archimedespunt af. Die hede, November 2011, is hierdie archimedespunt.

A few aspects regarding the reformed worship service and liturgical song in a multicultural South Africa. Worship originates within a specific culture. Because cultures are constantly changing and developing, the church also has to deal with change in its worship services. In postapartheid South Africa, with its variety of cultures, the reformed churches will increasingly have to take cognisance of the realities and issues brought about by its multicultural context. When focusing in this regard on one of the important acts in reformed worship, namely the liturgical song, some fascinating issues present themselves. It shows that the reformed churches in South Africa are indeed facing exceptional challenges. In the liturgical song God affords his church the perfect gift with which these challenges can be met. If handled in the Biblical way, the reality of a multicultural context becomes an opportunity to witness to the world the forgiveness and reconciliation through Jesus Christ.

A few aspects regarding the reformed worship service and liturgical song in a multicultural South Africa. Worship originates within a specific culture. Because cultures are constantly changing and developing, the church also has to deal with change in its worship services. In postapartheid South Africa, with its variety of cultures, the reformed churches will increasingly have to take cognisance of the realities and issues brought about by its multicultural context. When focusing in this regard on one of the important acts in reformed worship, namely the liturgical song, some fascinating issues present themselves. It shows that the reformed churches in South Africa are indeed facing exceptional challenges. In the liturgical song God affords his church the perfect gift with which these challenges can be met. If handled in the Biblical way, the reality of a multicultural context becomes an opportunity to witness to the world the forgiveness and reconciliation through Jesus Christ.

Well, spring, pit or whatever? b'r in the Masoretic text The Hebrew noun b'r is ojten in translations of the Bible translated with “well” although other translation equivalents, like “spring” and “pit”, are also used in some instances. The treatment of the word in a number of dictionaries for Biblical Hebrew is discussed (Koehler and Baumgartner, Brown, Driver and Briggs and the Theologisches Worterbuch zum Alten Testament). Five meanings of the word is defined The word is used for constructions made by man, and the following meanings are distinguished: a construction related to the exploitation of metals and minerals (“loam-pit”), a construction for the storage of spring water (“well”) a construction for getting access to subterranean water (“well”), a subterranean construction for the storage of rain water or grain (“cistern”), and a construction for burial (“grave”).

Well, spring, pit or whatever? b'r in the Masoretic text The Hebrew noun b'r is ojten in translations of the Bible translated with “well” although other translation equivalents, like “spring” and “pit”, are also used in some instances. The treatment of the word in a number of dictionaries for Biblical Hebrew is discussed (Koehler and Baumgartner, Brown, Driver and Briggs and the Theologisches Worterbuch zum Alten Testament). Five meanings of the word is defined The word is used for constructions made by man, and the following meanings are distinguished: a construction related to the exploitation of metals and minerals (“loam-pit”), a construction for the storage of spring water (“well”) a construction for getting access to subterranean water (“well”), a subterranean construction for the storage of rain water or grain (“cistern”), and a construction for burial (“grave”).

The authors study the influence of the vox pop~ as expressed by two proverbs (Ez 12:22 and 27; 18:2), on the structure of chapters 12 to 33. They conclude that Ezekiel 33 serves as a conclusion to this section, and forms a bridge to Ezekiel 34 onwards.

The authors study the influence of the vox pop~ as expressed by two proverbs (Ez 12:22 and 27; 18:2), on the structure of chapters 12 to 33. They conclude that Ezekiel 33 serves as a conclusion to this section, and forms a bridge to Ezekiel 34 onwards.