Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients

BackgroundChronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF.MethodsThis was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV₁), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection.ResultsA total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV₁, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09–2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65–4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant.ConclusionsBaseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression.     

Narrow-spectrum cephalosporin susceptibility testing of Escherichia coli with the BD Phoenix automated system: questionable utility of cephalothin as a predictor of cephalexin susceptibility

The resistance of Escherichia coli to cephalothin was found to be overestimated when the Phoenix automated susceptibility system was used to determine resistance compared to reference broth microdilution, a finding that jeopardized the use of cephalexin for first-line treatment of urinary tract infections in children. In addition, using broth microdilution, we studied the accuracy of either cephalothin or cefazolin in predicting cephalexin susceptibility. In contrast to the recommendation of the Clinical Laboratory Standards Institute (CLSI), we found that cephalothin is not a reliable predictor of cephalexin susceptibility. Cefazolin performs no better in this role. We suggest that laboratories should consider testing and reporting cefazolin and cephalexin independently, according to clinical need.     

Alberta infant motor scale: reliability and validity when used on preterm infants in Taiwan

BACKGROUND AND PURPOSE: The goal of this study was to examine the reliability and validity of measurements obtained with the Alberta Infant Motor Scale (AIMS) for evaluation of preterm infants in Taiwan. SUBJECTS: Two independent groups of preterm infants were used to investigate the reliability (n=45) and validity (n=41) for the AIMS. METHODS: In the reliability study, the AIMS was administered to the infants by a physical therapist, and infant performance was videotaped. The performance was then rescored by the same therapist and by 2 other therapists to examine the intrarater and interrater reliability. In the validity study, the AIMS and the Bayley Motor Scale were administered to the infants at 6 and 12 months of age to examine criterion-related validity. RESULTS: Intraclass correlation coefficients (ICCs) for intrarater and interrater reliability of measurements obtained with the AIMS were high (ICC=.97-.99). The AIMS scores correlated with the Bayley Motor Scale scores at 6 and 12 months (r=.78 and.90), although the AIMS scores at 6 months were only moderately predictive of the motor function at 12 months (r=.56). CONCLUSION AND DISCUSSION: The results suggest that measurements obtained with the AIMS have acceptable reliability and concurrent validity but limited predictive value for evaluating preterm Taiwanese infants.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.     

A Role Beyond Learning for NMDA Receptors in Reward-Based Decision-Making—a Pharmacological Study Using d-Cycloserine

N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA''s roles in neuronal super-additivity and as crucial for evidence integration for decisions.     

Holomorphic curves in surfaces of general type

This note answers some questions on holomorphic curves and their distribution in an algebraic surface of positive index. More specifically, we exploit the existence of natural negatively curved "pseudo-Finsler" metrics on a surface S of general type whose Chern numbers satisfy c(2)1>2c2 to show that a holomorphic map of a Riemann surface to S whose image is not in any rational or elliptic curve must satisfy a distance decreasing property with respect to these metrics. We show as a consequence that such a map extends over isolated punctures. So assuming that the Riemann surface is obtained from a compact one of genus q by removing a finite number of points, then the map is actually algebraic and defines a compact holomorphic curve in S. Furthermore, the degree of the curve with respect to a fixed polarization is shown to be bounded above by a multiple of q - 1 irrespective of the map.