Risque d’acquisition du virus de l’immunodéficience humaine (VIH) chez les femmes utilisant des hormones contraceptives orales et injectables

Objectif : Étudier l'association entre l’utilisation de contraceptifs hormonaux et le risque d'acquisition du VIH-1 chez les femmes au Malawi, en Afrique du Sud, en Zambie et au Zimbabwe. Devis : Analyses secondaires de 2887 femmes âgées de 17-55 ans ayant participé à l’étude HPTN 035, une étude de phase II/IIb sur l’efficacité de deux gels microbicides pour prévenir la transmission du VIH chez les femmes à risque. Méthodes : L'association entre l'utilisation de contraceptifs hormonaux et le risque d'acquisition du VIH-1 a été évaluée en utilisant des modèles de Cox. Des risques relatifs sont estimés où le groupe de référence est celui des femmes qui n’utilisent pas de contraceptifs hormonaux. De plus, un modèle multivarié de Cox est utilisé afin de contrôler pour les facteurs potentiellement confondants. Résultats : Les contraceptifs injectables ont été utilisés par 52,1% des femmes, alors que les contraceptifs oraux ont été utilisés par 20,7% de celles-ci. Pendant l'étude, il y a eu 192 séroconversions. L'incidence observée du VIH était de 2,28; 4,19 et 4,69 pour 100 personne-années pour les contraceptifs oraux, injectables et non hormonaux, respectivement. Lors de l’analyse multivariée, nous n'avons trouvé aucune association significative entre l’usage des contraceptifs hormonaux et l’acquisition du VIH-1. Le risque relatif ajusté (RRa) pour les contraceptifs oraux est de 0,573 (IC de 95% : [0,31-1,06]) et 0,981 (IC de 95% : [0,69 ; 1,39]) pour les contraceptifs injectables. Conclusions : Bien que cette étude ne démontre pas d’association entre l’usage des contraceptifs hormonaux et le VIH-1, nous concluons toutefois que ces méthodes de contraception ne protègent pas contre le VIH-1, et il est ainsi recommandé aux femmes utilisant des hormones contraceptives de toujours utiliser le condom pour prévenir l'infection au VIH-1.Objective: To investigate the association between the use of hormonal contraceptive and the risk of acquiring HIV-1 infection in women from Malawi, South Africa, Zambia and Zimbabwe. Design: Secondary analyses of 2887 women aged 17-55 years who participated in the HPTN 035 trial, a Phase II/IIb trial on the efficacy of two microbicide gels to prevent HIV transmission in women at risk in Africa. Methods: The association between the use of hormonal contraceptive and the risk of acquiring HIV-1 was evaluated using Cox proportionnal models. Relative risks of exposed women were estimated using as a reference group the women who do not use hormonal contraceptives. In addition, a multivariate Cox model was used to control for potentially confounding factors. Results: Injectable contraceptives were used by 52.1 % of women, while oral contraceptives were used by 20.7% of them. During the study, there were 192 seroconversions. The observed HIV-1 incidence was 2.28, 4.19 and 4.69 per 100 woman-years for oral, injectable and non-hormonal contraceptive users, respectively. In multivariate analysis, we found no significant association between the use of hormonal contraceptives and HIV-1 acquisition. The adjusted relative risk (aRR) for oral contraceptives was 0.573 (95% CI: [0.31 to 1.06]) and 0.981 (95% CI: [0.69, 1.39]) for injectable contraceptives. Conclusions: Although this study did not demonstrate an association between hormonal contraceptive use and the risk of HIV-1 infection, we conclude, however, that these methods of contraception do not protect against HIV-1, and it is thus recommended that women using contraceptive hormones always use condoms to prevent HIV-1

RETROSPEKTIVNA STUDIJA DENTAL TREATMENT OF CHILDREN WITH SPECIAL NEEDS UNDER GENERAL ANESTHESIA AT THE CLINIC OF DENTAL MEDICINE IN NIŠ - A TEN-YEAR RETROSPECTIVE STUDY

Introduction: The oral health of children with special needs is most often impaired, with a high prevalence of caries and its complications. Due to the impossibility of establishing an adequate child-dentist contact and a large number of carious teeth, dental treatment under general anesthesia is often indicated in this population of children. Aim: To perform a comprehensive analysis of the dental treatment of children with special needs under general anesthesia at the Clinic of Dental Medicine in Niš over a period of ten years. Material and methods: A retrospective study analyzed the dental documentation of children with special needs in whom dental treatment was performed under general anesthesia at the Clinic of Dental Medicine in Niš in the period from January 1, 2010 to December 31, 2019. Results: 286 children with special needs (14.7%) out of a total number of 1943 admitted at the Department for Preventive and Pediatric Dentistry of the Clinic of Dental Medicne in Niš during the analyzed period, originally from Nišava, Jablanica, Pčinja, Toplica, Rasina, and other administrative districts of Serbia, were treated under general anesthesia. In the second half of the ten-year follow-up period, almost twice as many children were treated regarding the first five years. The records show that 1754 teeth were restored, 28 endodontically treated, and 1417 extracted. Conclusion: A high percentage of children with special needs treated under general anesthesia and a constant increase in the number of such children in Southeastern Serbia suggest the need for close cooperation between dentists of health care centers in Southeastern Serbia and dentists at the Clinic of Dental Medicine in Niš, a tertiary dental health care center towards which patients of this part of Serbia gravitate

Hip osteoarthritis susceptibility is associated with IL1B −511(G>A) and IL1 RN (VNTR) genotypic polymorphisms in Croatian caucasian population

Among the predisposing factors to osteoarthritis (OA), a frequent destructive joint disease, is the complex genetic heritage including the interleukin‐1 family members like the IL1β (IL1B) and the IL1 receptor antagonist (IL1RN) genes. The aim of this study was to investigate allelic and genotypic frequencies of the IL1B gene single nucleotide polymorphism (SNP) at −511(G>A) and the variable number tandem repeat (VNTR) in the IL1RN gene in a Croatian Caucasian population of hip OA (HOA) cases and healthy controls. A total of 259 HOA patients with total hip replacement (THR) and 518 healthy blood donors as controls were genotyped for IL1B gene SNP −511(G>A) and the VNTR in the IL1RN gene associated with HOA. The genotype G/A (1/2) at IL1B was significantly associated with the protection of the HOA (p A) and IL1RN (VNTR) were found associated with the HOA. The haplotype 1–2 at these loci had only a trend to susceptibility (p = 0.065). Haplotype 1–3 had a significant male bias in diseased. Furthermore, genotype comprising 2–1/2–2 haplotypes was found significantly associated with predisposition to HOA (p = 0.027, OR = 2.23, 95% CI = 1.03–4.88), whereas genotype 1–1/2–2 with protection to disease (p = 0.028, OR = 0.65, 95% CI = 0.43–0.97). Our findings suggest that HOA in Croatian population might have a different genetic risk regarding the IL1 locus than has been reported for other Caucasian populations previously

A community-powered search of machine learning strategy space to find NMR property prediction models

The rise of machine learning (ML) has created an explosion in the potential strategies for using data to make scientific predictions. For physical scientists wishing to apply ML strategies to a particular domain, it can be difficult to assess in advance what strategy to adopt within a vast space of possibilities. Here we outline the results of an online community-powered effort to swarm search the space of ML strategies and develop algorithms for predicting atomic-pairwise nuclear magnetic resonance (NMR) properties in molecules. Using an open-source dataset, we worked with Kaggle to design and host a 3-month competition which received 47,800 ML model predictions from 2,700 teams in 84 countries. Within 3 weeks, the Kaggle community produced models with comparable accuracy to our best previously published "in-house" efforts. A meta-ensemble model constructed as a linear combination of the top predictions has a prediction accuracy which exceeds that of any individual model, 7-19x better than our previous state-of-the-art. The results highlight the potential of transformer architectures for predicting quantum mechanical (QM) molecular properties

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Curling i samtidens sken En djupdykning i marknadsföring och konsumentgrupper

Curling härstammar från Skottland och spåras tillbaka till 1500-talet. Curlingen kom till Sverige i mitten av 1800-talet och Svenska Curlingförbundet bildades i början av 1900-talet. Curlingsporten , som traditionellt förknippas med äldre vuxna, ölmagar, cigarettrökning och sällskaplighet, har gått in i en tid där dominerande diskurser främjar en strikt diet, lite alkohol, ingen rökning och konstant fysisk aktivitet som ett sätt att "åldras väl " inom sporten. Marknadsföring inom curling har blivit ett stort problem idag. Det här är en sport som ofta är okänd för allmänheten, men det finns många som älskar att spela det. Vidare kan man även se att bristen på information som ges till intresserade curlingfans är ett problem.  Syftet med studien är att undersöka hur curlingen ser ut i dagsläget. Mer specifikt hur marknadsföringen ser ut, men även vilka konsumentgrupper som i dagsläget förknippas med eller utövar sporten.  Resultatet i studien visar att det finns utvecklingsmöjligheter när det kommer till marknadsföring och konsumentgrupper inom curling. Dels arbete med sociala medier och vad som ska visas på dessa men även hur man ska locka fler ungdomar till sporten då den domineras av äldre individer.

Curling i samtidens sken En djupdykning i marknadsföring och konsumentgrupper

Curling härstammar från Skottland och spåras tillbaka till 1500-talet. Curlingen kom till Sverige i mitten av 1800-talet och Svenska Curlingförbundet bildades i början av 1900-talet. Curlingsporten , som traditionellt förknippas med äldre vuxna, ölmagar, cigarettrökning och sällskaplighet, har gått in i en tid där dominerande diskurser främjar en strikt diet, lite alkohol, ingen rökning och konstant fysisk aktivitet som ett sätt att "åldras väl " inom sporten. Marknadsföring inom curling har blivit ett stort problem idag. Det här är en sport som ofta är okänd för allmänheten, men det finns många som älskar att spela det. Vidare kan man även se att bristen på information som ges till intresserade curlingfans är ett problem.  Syftet med studien är att undersöka hur curlingen ser ut i dagsläget. Mer specifikt hur marknadsföringen ser ut, men även vilka konsumentgrupper som i dagsläget förknippas med eller utövar sporten.  Resultatet i studien visar att det finns utvecklingsmöjligheter när det kommer till marknadsföring och konsumentgrupper inom curling. Dels arbete med sociala medier och vad som ska visas på dessa men även hur man ska locka fler ungdomar till sporten då den domineras av äldre individer.