Cryptic silver resistance is prevalent and readily activated in certain Gram-negative pathogens

Objectives: To assess the prevalence of cryptic silver (Ag+) resistance amongst clinical isolates of Gram-negative bacteria, and to examine how overt Ag+ resistance becomes activated in such strains. Methods: Established methods were used to determine the susceptibility of 444 recent clinical isolates to Ag+, and to evaluate the potential for overt Ag+ resistance to emerge from these isolates by spontaneous mutation. The genetic basis for Ag+ resistance was investigated using PCR amplification and DNA sequencing. Results: None of the isolates tested displayed overt Ag+ resistance. However, upon silver challenge, high-level Ag+ resistance (silver nitrate MIC >128 mg/L) was selected at high frequency (10¯⁷ to 10¯⁸) in ˜76% isolates of Enterobacter spp., ˜58% isolates of Klebsiella spp., and ˜0.7% isolates of E. coli. All strains in which Ag+ resistance could be selected harboured the sil operon, with resistance in each case apparently resulting from activation of this system as a consequence of a single missense mutation in silS. By contrast, Ag+ resistance could not be selected in isolates lacking sil, which included all tested representatives of Acinetobacter baumannii, Pseudomonas aeruginosa, Proteus spp and Citrobacter spp. Conclusions: Whilst overt Ag+ resistance in Gram-negative pathogens is uncommon, cryptic Ag+ resistance pertaining to the sil operon is prevalent and readily activated in particular genera (Enterobacter and Klebsiella)

Hospitalized Children with 2009 Pandemic Influenza A (H1N1): Comparison to Seasonal Influenza and Risk Factors for Admission to the ICU

BACKGROUND: Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection. METHODS: We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008-09 seasonal influenza at The Children's Hospital, Denver, Colorado. RESULTS: Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008-09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS. CONCLUSIONS: Compared to the 2008-09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children

The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis

Dengue infection in adults has become increasingly common throughout the world. As most of the clinical features of dengue have been described in children, we undertook a prospective study to determine the early symptoms and signs of dengue in adults. We show here that, overall, dengue cases presented with high rates of symptoms listed in the WHO 1997 or 2009 classification schemes for probable dengue fever thus resulting in high sensitivities of these schemes when applied for early diagnosis. However, symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding were less frequently reported in older adults. This trend resulted in reduced sensitivity of the WHO classification schemes in older adults even though they showed increased risks of hospitalization and severe dengue. Instead, we suggest that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. This could be useful for early clinical diagnosis in older adults so that they can be monitored and treated for severe dengue, which is especially important when an antiviral drug becomes available

Automated segmentation of normal and diseased coronary arteries – The ASOCA challenge

Cardiovascular disease is a major cause of death worldwide. Computed Tomography Coronary Angiography (CTCA) is a non-invasive method used to evaluate coronary artery disease, as well as evaluating and reconstructing heart and coronary vessel structures. Reconstructed models have a wide array of for educational, training and research applications such as the study of diseased and non-diseased coronary anatomy, machine learning based disease risk prediction and in-silico and in-vitro testing of medical devices. However, coronary arteries are difficult to image due to their small size, location, and movement, causing poor resolution and artefacts. Segmentation of coronary arteries has traditionally focused on semi-automatic methods where a human expert guides the algorithm and corrects errors, which severely limits large-scale applications and integration within clinical systems. International challenges aiming to overcome this barrier have focussed on specific tasks such as centreline extraction, stenosis quantification, and segmentation of specific artery segments only. Here we present the results of the first challenge to develop fully automatic segmentation methods of full coronary artery trees and establish the first large standardized dataset of normal and diseased arteries. This forms a new automated segmentation benchmark allowing the automated processing of CTCAs directly relevant for large-scale and personalized clinical applications

Predicting Quantitative Genetic Interactions by Means of Sequential Matrix Approximation

Despite the emerging experimental techniques for perturbing multiple genes and measuring their quantitative phenotypic effects, genetic interactions have remained extremely difficult to predict on a large scale. Using a recent high-resolution screen of genetic interactions in yeast as a case study, we investigated whether the extraction of pertinent information encoded in the quantitative phenotypic measurements could be improved by computational means. By taking advantage of the observation that most gene pairs in the genetic interaction screens have no significant interactions with each other, we developed a sequential approximation procedure which ranks the mutation pairs in order of evidence for a genetic interaction. The sequential approximations can efficiently remove background variation in the double-mutation screens and give increasingly accurate estimates of the single-mutant fitness measurements. Interestingly, these estimates not only provide predictions for genetic interactions which are consistent with those obtained using the measured fitness, but they can even significantly improve the accuracy with which one can distinguish functionally-related gene pairs from the non-interacting pairs. The computational approach, in general, enables an efficient exploration and classification of genetic interactions in other studies and systems as well

Increased risk of cancer among relatives of patients with lung cancer in China

BACKGROUND: Genetic factors were considered as one of the risk factors for lung cancer or other cancers. The aim of this work was to determine whether a genetic predisposition accounts for such familial aggregation of cancer among relatives of lung cancer probands. METHODS: A case-control study was conducted in 800 case families identified by lung cancer patients (probands), and in 800 control families identified by the probands'spouses. The data were analysed with logistic regression analysis model. RESULTS: The data revealed a significantly greater overall risk of cancer (OR = 1.82, P < 0.01) in the proband group. The relatives of lung cancer probands maintained an increased risk of non-lung cancer (P < 0.05) after adjusting for confounder factors. The crude odds ratio of a proband family having one family member with cancer was 1.67 compared with control families. Proband families were 2.56 times more likely to have two other family members with cancer. For three cancers and four or more cancers, the risk increased to 3.50 and 5.91, respectively. The most striking differences in cancer prevalence between proband and control families were noted for cancer risk among female relatives. The strongest effects were for not only lung cancer in any female relatives (OR 2.17, 95%CI 1.60–3.64) and mothers (OR 2.78, 95%CI 1.23–5.12) and sisters (OR 2.03, 95%CI 1.26–3.97), but also non-lung cancer in females and mothers (OR 2.00, 95%CI 1.26–3.01, and OR 2.34, 95%CI 1.28–4.40, respectively). CONCLUSION: These data support the hypothesis of a genetic susceptibility to cancer in families with lung cancer, and the female genetic susceptibility to cancer might be greater than male

Investigating Crack Initiation and Propagation of Concrete in Restrained Shrinkage Circular/Elliptical Ring Test

The restrained ring test, which is recommended by AASHTO and ASTM, has been used for assessing the potential of early-age cracking of concrete and other cement-based materials. Recently, a novel elliptical ring test method has been proposed to replace the circular ring test method for the purpose of shortening ring test duration and observing crack initiation and propagation more conveniently. In order to explore the mechanism of this novel test method, a numerical model is developed to analyze crack initiation and propagation process in restrained concrete rings, in which the effect of concrete shrinkage is simulated by a fictitious temperature drop applied on concrete causing the same strain as that induced by shrinkage. First, an elastic analysis is conducted to obtain the circumferential stress contour of a concrete ring subject to restrained shrinkage. Combined with the fictitious crack model, a fracture mechanics method is introduced to determine crack initiation and propagation, in which crack resistance caused by cohesive force acting on fracture process zone is considered. Finite element analysis is carried out to simulate the evolution of stress intensity factor in restrained concrete rings subject to circumferential drying. Cracking age and position of a series of circular/elliptical concrete rings are obtained from numerical analyses which agree reasonably well with experimental results. It is found that the sudden drop of steel strain observed in the restrained ring test represents the onset of unstable crack propagation rather than crack initiation. The results given by the AASHTO/ASTM restrained ring test actually reflects the response of a concrete ring as a structure to external stimulation, in this case restrained concrete shrinkage.The financial support from the National Natural Science Foundation of China under the grants of NSFC 51478083 & 51421064, Engineering and Physical Sciences Research Council under the grant of EP/I031952/1, and the National Basic Research Program of China (973 Program, Grant No. 2015CB057703) is gratefully acknowledged