Potential Associations between Severity of Infection and the Presence of Virulence-Associated Genes in Clinical Strains of Staphylococcus aureus

BACKGROUND: The clinical spectrum of Staphylococcus aureus infection ranges from asymptomatic nasal carriage to osteomyelitis, infective endocarditis (IE) and death. In this study, we evaluate potential association between the presence of specific genes in a collection of prospectively characterized S. aureus clinical isolates and clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred thirty-nine S. aureus isolates (121 methicillin-resistant S. aureus [MRSA] and 118 methicillin-susceptible S. aureus [MSSA]) were screened by array comparative genomic hybridization (aCGH) to identify genes implicated in complicated infections. After adjustment for multiple tests, 226 genes were significantly associated with severity of infection. Of these 226 genes, 185 were not in the SCCmec element. Within the 185 non-SCCmec genes, 171 were less common and 14 more common in the complicated infection group. Among the 41 genes in the SCCmec element, 37 were more common and 4 were less common in the complicated group. A total of 51 of the 2014 sequences evaluated, 14 non-SCCmec and 37 SCCmec, were identified as genes of interest. CONCLUSIONS/SIGNIFICANCE: Of the 171 genes less common in complicated infections, 152 are of unknown function and may contribute to attenuation of virulence. The 14 non-SCCmec genes more common in complicated infections include bacteriophage-encoded genes such as regulatory factors and autolysins with potential roles in tissue adhesion or biofilm formation

The assessment and rehabilitation of prospective memory problems in people with neurological disorders: A review

People with neurological disorders often report difficulty with prospective memory (PM), that is, remembering to do things they had intended to do. This paper briefly reviews the literature regarding the neuropsychology of PM function, concluding that from the clinical perspective, PM is best considered in terms of its separable but interacting mnemonic and executive components. Next, the strengths and limitations in the current clinical assessment of PM, including the assessment of component processes, desktop analogues of PM tasks, and naturalistic PM tasks, are outlined. The evidence base for the rehabilitation of PM is then considered, focusing on retraining PM, using retrospective memory strategies, problem-solving training, and finally, electronic memory aids. It is proposed that further research should focus on establishing the predictive validity of PM assessment, and refining promising rehabilitation techniques

Calibration of the CMS hadron calorimeters using proton-proton collision data at root s=13 TeV

Methods are presented for calibrating the hadron calorimeter system of theCMSetector at the LHC. The hadron calorimeters of the CMS experiment are sampling calorimeters of brass and scintillator, and are in the form of one central detector and two endcaps. These calorimeters cover pseudorapidities vertical bar eta vertical bar ee data. The energy scale of the outer calorimeters has been determined with test beam data and is confirmed through data with high transverse momentum jets. In this paper, we present the details of the calibration methods and accuracy.Peer reviewe

Potential Associations between Severity of Infection and the Presence of Virulence-Associated Genes in Clinical Strains of Staphylococcus aureus

Abstract Background: The clinical spectrum of Staphylococcus aureus infection ranges from asymptomatic nasal carriage to osteomyelitis, infective endocarditis (IE) and death. In this study, we evaluate potential association between the presence of specific genes in a collection of prospectively characterized S. aureus clinical isolates and clinical outcome

Determination of an Inoculum Effect with Various Cephalosporins among Clinical Isolates of Methicillin-Susceptible Staphylococcus aureus▿

Using 98 clinical methicillin-susceptible Staphylococcus aureus isolates of known β-lactamase (Bla) type, we found a pronounced inoculum effect for cephalexin (mostly Bla type A and C strains), a mild inoculum effect for cephalothin (especially types B and C), and no inoculum effects for ceftriaxone and cefuroxime. Ceftobiprole showed the lowest MICs at a high inoculum but with a slight increase for Bla-positive versus Bla-negative strains. Since a potential therapeutic effect associated with a cephalosporin inoculum effect has been described, further studies are warranted

Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin-Susceptible Staphylococcus aureus: Frequency and Possible Cause of Cefazolin Treatment Failure▿

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A β-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC90 was 2 μg/ml for a standard inoculum and 32 μg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of ≥16 μg/ml with 107 CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses

Controlling X-rays With Light

Ultrafast x-ray science is an exciting frontier that promises the visualization of electronic, atomic and molecular dynamics on atomic time and length scales. A largelyunexplored area of ultrafast x-ray science is the use of light to control how x-rays interact with matter. In order to extend control concepts established for long wavelengthprobes to the x-ray regime, the optical control field must drive a coherent electronic response on a timescale comparable to femtosecond core-hole lifetimes. An intense field is required to achieve this rapid response. Here an intense optical control pulse isobserved to efficiently modulate photoelectric absorption for x-rays and to create an ultrafast transparency window. We demonstrate an application of x-ray transparencyrelevant to ultrafast x-ray sources: an all-photonic temporal cross-correlation measurement of a femtosecond x-ray pulse. The ability to control x-ray/matterinteractions with light will create new opportunities at current and next-generation x-ray light sources