Serum (1 → 3)-β-d-glucan measurement as an early indicator of Pneumocystis jirovecii pneumonia and evaluation of its prognostic value

AbstractPneumocystis jirovecii (carinii) pneumonia (PJP) is a major cause of disease in immunocompromised individuals. However, until recently no reliable and specific serological parameters for the diagnosis of PJP have been available. (1 → 3)-β-d-Glucan (BG) is a cell wall component of P. jirovecii and of various other fungi. Data from the past few years have pointed to serum measurement of BG as a promising new tool for the diagnosis of PJP. We therefore conducted a retrospective study on 50 patients with PJP and 50 immunocompromised control patients to evaluate the diagnostic performance of serum BG measurement. Our results show an excellent diagnostic performance with a sensitivity of 98.0% and a specificity of 94%. While the positive predictive value was only 64.7%, the negative predictive value was 99.8% and therefore a negative BG result almost rules out PJP. BG levels were already strongly elevated in an average of 5 days and up to 21 days before microbiological diagnosis demonstrating that the diagnosis could have been confirmed earlier. BG levels at diagnosis and maximum BG levels during follow-up did not correlate with the outcome of patients or with the P. jirovecii burden in the lung as detected by Real-Time PCR. Therefore, absolute BG levels seem to be of no prognostic value. Altogether, BG is a reliable parameter for the diagnosis of PJP and could be used as a preliminary test for patients at risk before a bronchoalveolar lavage is performed

Partial Transmutation of Singularities in Optical Instruments

Some interesting optical instruments such as the Eaton lens and the Invisible Sphere require singularities of the refractive index for their implementation. We show how to transmute those singularities into harmless topological defects in anisotropic media without the need for anomalous material properties

Coherent vs incoherent interlayer transport in layered metals

The magnetic-field, temperature, and angular dependence of the interlayer magnetoresistance of two different quasi-two-dimensional (2D) organic superconductors is reported. For $\kappa$-(BEDT-TTF)$_2$I$_3$ we find a well-resolved peak in the angle-dependent magnetoresistance at $\Theta = 90^\circ$ (field parallel to the layers). This clear-cut proof for the coherent nature of the interlayer transport is absent for $\beta$''-(BEDT-TTF)$_2$SF$_5$CH$_2$CF$_2$SO$_3$. This and the non-metallic behavior of the magnetoresistance suggest an incoherent quasiparticle motion for the latter 2D metal.Comment: 4 pages, 4 figures. Phys. Rev. B, in pres

User needs elicitation via analytic hierarchy process (AHP). A case study on a Computed Tomography (CT) scanner

Background: The rigorous elicitation of user needs is a crucial step for both medical device design and purchasing. However, user needs elicitation is often based on qualitative methods whose findings can be difficult to integrate into medical decision-making. This paper describes the application of AHP to elicit user needs for a new CT scanner for use in a public hospital. Methods: AHP was used to design a hierarchy of 12 needs for a new CT scanner, grouped into 4 homogenous categories, and to prepare a paper questionnaire to investigate the relative priorities of these. The questionnaire was completed by 5 senior clinicians working in a variety of clinical specialisations and departments in the same Italian public hospital. Results: Although safety and performance were considered the most important issues, user needs changed according to clinical scenario. For elective surgery, the five most important needs were: spatial resolution, processing software, radiation dose, patient monitoring, and contrast medium. For emergency, the top five most important needs were: patient monitoring, radiation dose, contrast medium control, speed run, spatial resolution. Conclusions: AHP effectively supported user need elicitation, helping to develop an analytic and intelligible framework of decision-making. User needs varied according to working scenario (elective versus emergency medicine) more than clinical specialization. This method should be considered by practitioners involved in decisions about new medical technology, whether that be during device design or before deciding whether to allocate budgets for new medical devices according to clinical functions or according to hospital department

Magic angle effects of the one-dimensional axis conductivity in quasi-one dimensional conductors

In quasi-one-dimensional conductors, the conductivity in both one-dimensional axis and interchain direction shows peaks when magnetic field is tilted at the magic angles in the plane perpendicular to the conducting chain. Although there are several theoretical studies to explain the magic angle effect, no satisfactory explanation, especially for the one-dimensional conductivity, has been obtained. We present a new theory of the magic angle effect in the one-dimensional conductivity by taking account of the momentum-dependence of the Fermi velocity, which should be large in the systems close to a spin density wave instability. The magic angle effect is explained in the semiclassical equations of motion, but neither the large corrugation of the Fermi surface due to long-range hoppings nor hot spots, where the relaxation time is small, on the Fermi surface are required.Comment: 4 pages, 3 figure

Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation

Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch

Magnetic-Field Variations of the Pair-Breaking Effects of Superconductivity in (TMTSF)2ClO4

We have studied the onset temperature of the superconductivity Tc_onset of the organic superconductor (TMTSF)2ClO4, by precisely controlling the direction of the magnetic field H. We compare the results of two samples with nearly the same onset temperature but with different scattering relaxation time tau. We revealed a complicated interplay of a variety of pair-breaking effects and mechanisms that overcome these pair-breaking effects. In low fields, the linear temperature dependences of the onset curves in the H-T phase diagrams are governed by the orbital pair-breaking effect. The dips in the in-plane field-angle phi dependence of Tc_onset, which were only observed in the long-tau sample, provides definitive evidence that the field-induced dimensional crossover enhances the superconductivity if the field direction is more than about 19-degrees away from the a axis. In the high-field regime for H//a, the upturn of the onset curve for the long-tau sample indicates a new superconducting state that overcomes the Pauli pair-breaking effect but is easily suppressed by impurity scatterings. The Pauli effect is also overcome for H//b' by a realization of another state for which the maximum of Tc_onset(phi) occurs in a direction different from the crystalline axes. The effect on Tc_onset of tilting the applied field out of the conductive plane suggests that the Pauli effect plays a significant role in determining Tc_onset. The most plausible explanation of these results is that (TMTSF)2ClO4 is a singlet superconductor and exhibits Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) states in high fields.Comment: 12 pages, 10 figures. To be published in J. Phys. Soc. Jpn. (vol.77, 2008

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer

Introduction/backgroundPhosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer.Methods/materialsPatients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant.ResultsNinety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively.ConclusionERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial