Antimicrobial resistance in community and nosocomial Escherichia coli urinary tract isolates, London 2005 – 2006

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>is the commonest cause of community and nosocomial urinary tract infection (UTI). Antibiotic treatment is usually empirical relying on susceptibility data from local surveillance studies. We therefore set out to determine levels of resistance to 8 commonly used antimicrobial agents amongst all urinary isolates obtained over a 12 month period.</p> <p>Methods</p> <p>Antimicrobial susceptibility to ampicillin, amoxicillin/clavulanate, cefalexin, ciprofloxacin, gentamicin, nitrofurantoin, trimethoprim and cefpodoxime was determined for 11,865 <it>E. coli </it>urinary isolates obtained from community and hospitalised patients in East London.</p> <p>Results</p> <p>Nitrofurantoin was the most active agent (94% susceptible), followed by gentamicin and cefpodoxime. High rates of resistance to ampicillin (55%) and trimethoprim (40%), often in combination were observed in both sets of isolates. Although isolates exhibiting resistance to multiple drug classes were rare, resistance to cefpodoxime, indicative of Extended spectrum β-lactamase production, was observed in 5.7% of community and 21.6% of nosocomial isolates.</p> <p>Conclusion</p> <p>With the exception of nitrofurantoin, resistance to agents commonly used as empirical oral treatments for UTI was extremely high. Levels of resistance to trimethoprim and ampicillin render them unsuitable for empirical use. Continued surveillance and investigation of other oral agents for treatment of UTI in the community is required.</p

Genotyping Performance Assessment of Whole Genome Amplified DNA with Respect to Multiplexing Level of Assay and Its Period of Storage

Whole genome amplification can faithfully amplify genomic DNA (gDNA) with minimal bias and substantial genome coverage. Whole genome amplified DNA (wgaDNA) has been tested to be workable for high-throughput genotyping arrays. However, issues about whether wgaDNA would decrease genotyping performance at increasing multiplexing levels and whether the storage period of wgaDNA would reduce genotyping performance have not been examined. Using the Sequenom MassARRAY iPLEX Gold assays, we investigated 174 single nucleotide polymorphisms for 3 groups of matched samples: group 1 of 20 gDNA samples, group 2 of 20 freshly prepared wgaDNA samples, and group 3 of 20 stored wgaDNA samples that had been kept frozen at −70°C for 18 months. MassARRAY is a medium-throughput genotyping platform with reaction chemistry different from those of high-throughput genotyping arrays. The results showed that genotyping performance (efficiency and accuracy) of freshly prepared wgaDNA was similar to that of gDNA at various multiplexing levels (17-plex, 21-plex, 28-plex and 36-plex) of the MassARRAY assays. However, compared with gDNA or freshly prepared wgaDNA, stored wgaDNA was found to give diminished genotyping performance (efficiency and accuracy) due to potentially inferior quality. Consequently, no matter whether gDNA or wgaDNA was used, better genotyping efficiency would tend to have better genotyping accuracy

A Deletion in Exon 9 of the LIPH Gene Is Responsible for the Rex Hair Coat Phenotype in Rabbits (Oryctolagus cuniculus)

The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the “r1” mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Z = 78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits

A Deletion in Exon 9 of the LIPH Gene Is Responsible for the Rex Hair Coat Phenotype in Rabbits (Oryctolagus cuniculus)

The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the “r1” mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Z = 78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits

Large Scale Association Analysis Identifies Three Susceptibility Loci for Coronary Artery Disease

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology

Probing Real Sensory Worlds of Receivers with Unsupervised Clustering

The task of an organism to extract information about the external environment from sensory signals is based entirely on the analysis of ongoing afferent spike activity provided by the sense organs. We investigate the processing of auditory stimuli by an acoustic interneuron of insects. In contrast to most previous work we do this by using stimuli and neurophysiological recordings directly in the nocturnal tropical rainforest, where the insect communicates. Different from typical recordings in sound proof laboratories, strong environmental noise from multiple sound sources interferes with the perception of acoustic signals in these realistic scenarios. We apply a recently developed unsupervised machine learning algorithm based on probabilistic inference to find frequently occurring firing patterns in the response of the acoustic interneuron. We can thus ask how much information the central nervous system of the receiver can extract from bursts without ever being told which type and which variants of bursts are characteristic for particular stimuli. Our results show that the reliability of burst coding in the time domain is so high that identical stimuli lead to extremely similar spike pattern responses, even for different preparations on different dates, and even if one of the preparations is recorded outdoors and the other one in the sound proof lab. Simultaneous recordings in two preparations exposed to the same acoustic environment reveal that characteristics of burst patterns are largely preserved among individuals of the same species. Our study shows that burst coding can provide a reliable mechanism for acoustic insects to classify and discriminate signals under very noisy real-world conditions. This gives new insights into the neural mechanisms potentially used by bushcrickets to discriminate conspecific songs from sounds of predators in similar carrier frequency bands

Research priority setting in emergency care: A scoping review

ObjectivePriority areas for emergency care research are emerging and becoming ever more important. The objectives of this scoping review were to (1) provide a comprehensive overview of published emergency care priority-setting studies by collating and comparing priority-setting methodology and (2) describe the resulting research priorities identified. MethodsThe Joanna Briggs Institute methodological framework was used. Inclusion criteria were peer-review articles available in English, published between January 1, 2008 and March 31, 2019 and used 2 or more search terms. Five databases (Scopus, AustHealth, EMBASE, CINAHL, and Ovid MEDLINE) were searched. REporting guideline for PRIority SEtting of health research (REPRISE) criteria were used to assess the quality of evidence of included articles. ResultsForty-five studies were included. Fourteen themes for emergency care research were considered within 3 overarching research domains: emergency populations (pediatrics, geriatrics), emergency care workforce and processes (nursing, shared decision making, general workforce, and process), and emergency care clinical areas (imaging, falls, pain management, trauma care, substance misuse, infectious diseases, mental health, cardiology, general clinical care). Variation in the reporting of research priority areas was evident. Priority areas to drive the global agenda for emergency care research are limited given the country and professional group-specific context of existing studies. ConclusionThis comprehensive summary of generated research priorities across emergency care provides insight into current and future research agendas. With the nature of emergency care being inherently broad, future priorities may warrant population (eg, children, geriatrics) or subspecialty (eg, trauma, toxicology, mental health) focus and be derived using a rigorous framework and patient engagement

Bloodstream infection due to Acinetobacter spp: Epidemiology, risk factors and impact of multi-drug resistance

Acinetobacter spp. are increasingly reported as important causes of human infection. Many isolates exhibit multi-drug resistance, raising concerns over our ability to treat serious infections with these organisms. The impact of infection on clinical outcome as well as the importance of multi-drug resistance is poorly defined. A descriptive retrospective observational study was undertaken of all episodes of Acinetobacter bacteremia occurring in a UK tertiary care centre from 1998-2006. Demographics of infected patients, characteristics and antimicrobial susceptibility of infecting strains were recorded and the impact of antimicrobial therapy on all causes of 30-day mortality assessed. Three hundred ninety-nine episodes of Acinetobacter bacteremia were identified, with A. baumannii being the most frequently isolated species. Most episodes occurred in critical care and were associated with multidrug resistance, with carbapenem resistance rising from 0% in 1998 to 55% in 2006. Although bacteremia due to carbapenem-resistant Acinetobacter and a requirement for critical care were associated with a higher mortality, mortality was not reduced by the administration of appropriate empirical antimicrobial therapy. A prospective study is required to identify both the most effective intervention and those most likely to benefit from treatment.C

Research priority setting in emergency care : A scoping review

Objective: Priority areas for emergency care research are emerging and becoming ever more important. The objectives of this scoping review were to (1) provide a comprehensive overview of published emergency care priority-setting studies by collating and comparing priority-setting methodology and (2) describe the resulting research priorities identified. Methods: The Joanna Briggs Institute methodological framework was used. Inclusion criteria were peer-review articles available in English, published between January 1, 2008 and March 31, 2019 and used 2 or more search terms. Five databases (Scopus, AustHealth, EMBASE, CINAHL, and Ovid MEDLINE) were searched. REporting guideline for PRIority SEtting of health research (REPRISE) criteria were used to assess the quality of evidence of included articles. Results: Forty-five studies were included. Fourteen themes for emergency care research were considered within 3 overarching research domains: emergency populations (pediatrics, geriatrics), emergency care workforce and processes (nursing, shared decision making, general workforce, and process), and emergency care clinical areas (imaging, falls, pain management, trauma care, substance misuse, infectious diseases, mental health, cardiology, general clinical care). Variation in the reporting of research priority areas was evident. Priority areas to drive the global agenda for emergency care research are limited given the country and professional group-specific context of existing studies. Conclusion: This comprehensive summary of generated research priorities across emergency care provides insight into current and future research agendas. With the nature of emergency care being inherently broad, future priorities may warrant population (eg, children, geriatrics) or subspecialty (eg, trauma, toxicology, mental health) focus and be derived using a rigorous framework and patient engagement