A survey on hospitalised community-acquired pneumonia in Italy.

Background and aim. Community Acquired Pneumonia (CAP) remains a major cause of disease and death. We evaluated the levels of care, the outcome and the characteristics of hospitalised patients with CAP in a primary hospital in Italy. We also investigated the value of both the Pneumonia Severity Index (PSI) and the modified Appropriateness Evaluation Protocol (AEP) for recognising both the outcome and the unnecessary admissions and stay of hospitalised patients with CAP. Methods. A retrospective review of all the charts of adult patients with CAP at Manerbio, Brescia, Italy between January 2001 and December 2002 was performed. Results. We evaluated 148 patients; their mean age (±SD) was 70 (±17) years; 34% were female. Most patients (87%) had at least a concomitant co-morbid disease. The overall survival rate at 30 days was 88%. All but one death occurred in the high-risk group of patients according to the PSI. On the contrary, the death rate of patients with inappropriate hospital admission according to the AEP was high. Patients with high PSI score had a significantly longer hospital length of stay than the low-risk group. However, a substantial part of the hospital stay did not show any justification into the charts. Conclusions. The PSI, but not the AEP, upon hospital admission, was useful for evaluating the outcome of patients with CAP. The PSI score and the modified AEP can be useful for assessing the appropriateness of hospitalisation for patients with CAP. There is the need for a practical and validated tool to support physicians in their decision making regarding the early and safe discharge of hospitalised patients with CAP

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.

Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypicallyestimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P=7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O. R.=1.12; P=3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O. R.=1.14; 95% C. I.=1.03-1.28) and TERT (O. R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O. R.=1.18; 95% C. I.=1.05-1.33) and CTC1 (O. R.=1.14; 95% C. I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis

Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors

BACKGROUND The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. METHODS We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants. RESULTS Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants. CONCLUSIONS Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. (Funded by the National Institutes of Health and others.

CMS physics technical design report: Addendum on high density QCD with heavy ions

This report presents the capabilities of the CMS experiment to explore the rich heavy-ion physics programme offered by the CERN Large Hadron Collider (LHC). The collisions of lead nuclei at energies ,will probe quark and gluon matter at unprecedented values of energy density. The prime goal of this research is to study the fundamental theory of the strong interaction - Quantum Chromodynamics (QCD) - in extreme conditions of temperature, density and parton momentum fraction (low-x). This report covers in detail the potential of CMS to carry out a series of representative Pb-Pb measurements. These include "bulk" observables, (charged hadron multiplicity, low pT inclusive hadron identified spectra and elliptic flow) which provide information on the collective properties of the system, as well as perturbative probes such as quarkonia, heavy-quarks, jets and high pT hadrons which yield "tomographic" information of the hottest and densest phases of the reaction.0info:eu-repo/semantics/publishe