Risk factors for positive follow-up blood cultures in critically ill adults with Gram-negative bacteraemia.

Objectives: To evaluate the utility of follow-up blood cultures (FUBCs) for Gram-negative bloodstream infection (BSI) in ICU patients and identify risk factors for repeat positive cultures.

Methods: This was a single-centre, retrospective cohort study of critically ill adults with Gram-negative BSI between 1 January 2015 and 1 January 2020. Critically ill patients with one or more blood cultures positive for a Gram-negative organism were included.

Evaluation of Ceftazidime Use in the Neonatal Intensive Care Unit and Association With Cephalosporin-Resistant Gram-Negative Bacteria.

Background: Cefotaxime shortage in 2015 led to increased ceftazidime use in the neonatal intensive care unit (NICU).

Objective: The purpose was to explore whether ceftazidime increases risk for development of resistant gram-negative organisms.

Methods: Retrospective evaluation of NICU patients with cultures positive for , , species, or between January1, 2015 and August 31, 2020.

Ketamine infusions as an adjunct for sedation in critically ill children.

Objective: Limited reports have described ketamine's role as an adjunct sedative. The purpose was to describe ketamine's role as an adjunct to achieve goal sedation in mechanically ventilated children.

Design: Retrospective, descriptive study.

Extended Duration Ketamine Infusions in Critically Ill Children: A Case Report and Review of the Literature.

Ketamine is an -methyl-D-aspartate receptor antagonist that has been used as an adjunct analgesic and sedative in critically ill children. Previous reports noted that ketamine has been used for a variable duration of 12 to 408 hours for this indication. We report on the use of ketamine infusions for >720 hours as a second-line sedative in addition to an opioid and dexmedetomidine infusion in a 2-month old and 17-month old.

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3.

Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?

In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors.

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.

Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women.

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one.

Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study.

Background: Germline pathogenic variants in the E-cadherin gene (CDH1) are strongly associated with the development of hereditary diffuse gastric cancer. There is a paucity of data to guide risk assessment and management of families with hereditary diffuse gastric cancer that do not carry a CDH1 pathogenic variant, making it difficult to make informed decisions about surveillance and risk-reducing surgery. We aimed to identify new candidate genes associated with predisposition to hereditary diffuse gastric cancer in affected families without pathogenic CDH1 variants.

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.

A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity.

Background And Purpose: This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2years after radiotherapy.

Materials And Methods: A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression.

Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.

Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance.

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.

The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism.

The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb.

The complete genome sequence of Mycobacterium bovis.

Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M.