ISSUES CONCERNING TRIPOLYE METALLURGY AND THE VIRGIN COPPER OF VOLHYNIA

The ‘western borderland’ of the Tripolye culture, appearing in the title of this volume of the ‘Baltic-Pontic Studies’, refers to the cyrcle of neighbouring cultural systems of the Upper Tisza and Vistula drainages. As neighbours of the Tripolye culture such groups are discussed as Lengyel-Polg´ar, Funnel Beaker and, albeit to a much narrower extent, the Globular Amphora (cf. B-PS vol. 8) and the Corded Ware cultures. The papers discuss the reception of ‘western’ traditions by Tripolye communities as well as the ‘western borderland’ mentioned in the title. Defined in this way, these questions have been only cursorily treated in the literature. The consequences of accumulated omissions in the study of the cultural surroundings of ‘Tripolye’ have been felt by us when we worked on this issue. Thus, we submit a greatly limited work as far as its subject matter is concerned hoping that it will open a sequence of necessary studies. Such studies should, in the first place, focus on the co-ordination of the ‘languages’ of taxonomy and then they should investigate different aspects of the mechanisms of the outlined processes of the ‘cultural contact’

ISSUES CONCERNING TRIPOLYE METALLURGY AND THE VIRGIN COPPER OF VOLHYNIA

The ‘western borderland’ of the Tripolye culture, appearing in the title of this volume of the ‘Baltic-Pontic Studies’, refers to the cyrcle of neighbouring cultural systems of the Upper Tisza and Vistula drainages. As neighbours of the Tripolye culture such groups are discussed as Lengyel-Polg´ar, Funnel Beaker and, albeit to a much narrower extent, the Globular Amphora (cf. B-PS vol. 8) and the Corded Ware cultures. The papers discuss the reception of ‘western’ traditions by Tripolye communities as well as the ‘western borderland’ mentioned in the title. Defined in this way, these questions have been only cursorily treated in the literature. The consequences of accumulated omissions in the study of the cultural surroundings of ‘Tripolye’ have been felt by us when we worked on this issue. Thus, we submit a greatly limited work as far as its subject matter is concerned hoping that it will open a sequence of necessary studies. Such studies should, in the first place, focus on the co-ordination of the ‘languages’ of taxonomy and then they should investigate different aspects of the mechanisms of the outlined processes of the ‘cultural contact’

Patterns of HIV-1 drug resistance among HIV-infected patients receiving first-line antiretroviral therapy in Novosibirsk Region, Russia

ABSTRACT: Objectives: Antiretroviral (ARV) drugs have played a vital role in controlling the HIV-1 epidemic; however, some challenges remain. ARV drugs vary in their ability to control HIV infection, displaying differences in treatment-limiting factors and genetic barriers to resistance. The current report assesses the prevalence of HIV-1 drug resistance mutations (DRMs) among patients who failed first-line antiretroviral therapy (ART) and evaluates the genetic barrier of different regimens. Methods: The study cohort (n = 271) included HIV-infected individuals who visited the Novosibirsk, Russia, HIV/AIDS clinic in 2018–2022. All patients received first-line ART prior to virological failure. Sociodemographic and HIV-related data were collected from medical records and self-reported questionnaires. HIV-1 pol gene sequences were generated, and the presence of HIV-1 DRM was assessed. The genetic barrier to resistance was assessed by combining treatment regimen and adherence data. Results: Nonoptimal ART adherence was identified in 48.3% of patients and correlated with male sex, PWID, unemployment, and rural area residence. Most of the patients with high-level adherence were identified among those who were on TDF+3TC+DTG. HIV-1 DRMs were identified in 54.6% of the patients. The analysis of HIV-1 DRM, ART regimen, and adherence data classified TDF+3TC+DTG and TDF+3TC+LPV/r as treatment regimens with a high genetic barrier, whereas EFV-containing ART was classified as a regimen with a low genetic barrier. Conclusions: The current study delivers results on the efficacy of HIV-1 ART and treatment adherence in real-world practice settings. This report suggests that ART regimens with a high genetic barrier to resistance combined with improved treatment adherence may reduce the transmission of HIV-1 resistant variants

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk