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Purpose To identify the attributable mortality of central line associated blood stream infections (CLABSI) through meta-analysis. Methods Meta-analysis of case control and cohort studies, matched and unmatched, that reported on mortality of patients with and without CLABSI was performed. MEDLINE, CENTRAL, CINAHL were searched. Non-interventional studies of all languages that reported mortality in patients with CLABSI were included. Data were extracted on patient population, study setting, design, diagnostic criteria for CLABSI, and mortality. Results from studies comparing mortality due to CLABSI were pooled using a random effects model with assessment of heterogeneity. Heterogeneity of studies was assessed with an I 2 statistic and a funnel plot was generated to assess for publication bias. Results Eighteen studies were included with 1,976 CLABSI cases. Of the included studies, 17 took place in intensive care unit settings, most involved a mixed population of medical and surgical patients, and ten were matched using an illness severity index. Our findings show an odds ratio of in hospital death associated with CLABSI as 2.75 (CI 1.86–4.07) and 1.51 (CI 1.08–2.09) in the subgroup of the ten matched studies. Those studies where greater than 30 % of CLABSI were attributed to coagulase-negative Staphylococcus had an odds ratio of death of 1.64 (95 % CI 1.02–2.65) compared with 4.71 (95 % CI 1.54–14.39). Conclusions CLABSI is associated with a significantly increased risk of death supporting the use of extensive efforts to reduce these infections.

In the field of beam physics, two frontier topics have taken center stage due to their potential to enable new approaches to discovery in a wide swath of science. These areas are: advanced, high gradient acceleration techniques, and x-ray free electron lasers (XFELs). Further, there is intense interest in the marriage of these two fields, with the goal of producing a very compact XFEL. In this context, recent advances in high gradient radio-frequency cryogenic copper structure research have opened the door to the use of surface electric fields between 250 and 500 MV m−1. Such an approach is foreseen to enable a new generation of photoinjectors with six-dimensional beam brightness beyond the current state-of-the-art by well over an order of magnitude. This advance is an essential ingredient enabling an ultra-compact XFEL (UC-XFEL). In addition, one may accelerate these bright beams to GeV scale in less than 10 m. Such an injector, when combined with inverse free electron laser-based bunching techniques can produce multi-kA beams with unprecedented beam quality, quantified by 50 nm-rad normalized emittances. The emittance, we note, is the effective area in transverse phase space (x, p x /m e c) or (y, p y /m e c) occupied by the beam distribution, and it is relevant to achievable beam sizes as well as setting a limit on FEL wavelength. These beams, when injected into innovative, short-period (1-10 mm) undulators uniquely enable UC-XFELs having footprints consistent with university-scale laboratories. We describe the architecture and predicted performance of this novel light source, which promises photon production per pulse of a few percent of existing XFEL sources. We review implementation issues including collective beam effects, compact x-ray optics systems, and other relevant technical challenges. To illustrate the potential of such a light source to fundamentally change the current paradigm of XFELs with their limited access, we examine possible applications in biology, chemistry, materials, atomic physics, industry, and medicine-including the imaging of virus particles-which may profit from this new model of performing XFEL science.

We study a class of Markov chains that model the evolution of a quantum system subject to repeated measurements. Each Markov chain in this class is defined by a measure on the space of matrices, and is then given by a random product of correlated matrices taken from the support of the defining measure. We give natural conditions on this support that imply that the Markov chain admits a unique invariant probability measure. We moreover prove the geometric convergence towards this invariant measure in the Wasserstein metric. Standard techniques from the theory of products of random matrices cannot be applied under our assumptions, and new techniques are developed, such as maximum likelihood-type estimations.

s Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson’s disease (PD). This study examined, in a descriptive manner, the correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1β, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1β release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central pathology.

Intense femtosecond x-ray pulses from free-electron laser sources allow the imaging of individual particles in a single shot. Early experiments at the Linac Coherent Light Source (LCLS) have led to rapid progress in the field and, so far, coherent diffractive images have been recorded from biological specimens, aerosols, and quantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLS held a workshop to discuss the scientific and technical challenges for reaching the ultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap toward reaching atomic resolution, 3D imaging at free-electron laser sources.

lung perfusion (EVLP) is a technique for graft preservation, evaluation and treatment, that could expand donor pool for transplantation. Nevertheless, the wide spectrum of available platforms has generated disparities in use, outcome, and costs. This study is an attempt to create a national consensus on EVLP use by a group of experts from the Italian Society of Organ Transplantation. The 9-member promoting committee was divided into 3 groups to propose statements. Using the DELPHI method 27 experts (three from each of the 9 lung transplant centres) voted agreement to each statement in 3 rounds. The cutoff for acceptance was set at 80% agreement. In the first vote, 52 statements were proposed, and an agreement was reached for 20 of them (38%). After revision, the second round resulted in a quorum for 36 out of 40 statements proposed (90%). At the third vote, agreement was confirmed for 36 statements (8 indications for use, 19 modalities for use, 13 evaluation parameters). The statements outlined in this document do not represent absolute guidelines, but rather recommendations. The statements selected and presented are therefore aimed to assist Italian clinicians in the use of an normothermic perfusion platform in the right context.

In this paper we present undulator magnet tapering methods for obtaining high efficiency and multiterawatt peak powers in x-ray free electron lasers (XFELs), a key requirement for enabling 3D atomic resolution single molecule imaging and nonlinear x-ray science. The peak power and efficiency of tapered XFELs is sensitive to time dependent effects, like synchrotron sideband growth. To analyze this dependence in detail we perform a comparative numerical optimization for the undulator magnetic field tapering profile including and intentionally disabling these effects. We show that the solution for the magnetic field taper profile obtained from time independent optimization does not yield the highest extraction efficiency when time dependent effects are included. Our comparative optimization is performed for a novel undulator designed specifically to obtain TW power x-ray pulses in the shortest distance: superconducting, helical, with short period and built-in strong focusing. This design reduces the length of the breaks between modules, decreasing diffraction effects, and allows using a stronger transverse electron focusing. Both effects reduce the gain length and the overall undulator length. We determine that after a fully time dependent optimization of a 100 m long Linac coherent light source-like XFEL we can obtain a maximum efficiency of 7%, corresponding to 3.7 TW peak radiation power. Possible methods to suppress the synchrotron sidebands, and further enhance the FEL peak power, up to about 6 TW by increasing the seed power and reducing the electron beam energy spread, are also discussed.

The standard Heller myotomy (SM) for achalasia extends 1 to 2 cm on to the stomach. The authors perform an extended myotomy (EM) (>3 cm) with the goal of reducing postoperative dysphagia. This study examines the long-term efficacy and durability of EM compared with SM. Patients with achalasia who underwent a laparoscopic Heller myotomy were identified from a prospective database that includes symptom evaluation and results of esophageal functional studies. From September 1994 to August 1998, the authors performed SM with Dor fundoplication, and from September 1998 through 2003, they performed EM with Toupet fundoplication. In 2001, they performed a telephone survey of all available patients. This was repeated in 2005 for the EM group. The survey included scales of symptom frequency (0 [never], 1 [once per month], 2 [once per week], 3 [once per day], 4 [more than once per day]) and severity (0 [no symptoms] to 10 [symptoms equal to preoperative state]) as well as the need to undergo postoperative intervention for dysphagia. For this study, 52 patients underwent SM with Dor fundoplication (median follow-up period, 46 +/- 24 months), and 63 patients underwent EM with Toupet fundoplication (median follow-up period, 45 +/- 17 months. Postoperative dysphagia severity was significantly better in the EM group (4.8 +/- 2.3 vs 3.1 +/- 2.6; p < 0.005). There was no significant difference in postoperative heartburn frequency, esophageal acid exposure, or lower esophageal sphincter pressure. In the SM group, 9 patients (17%) required reintervention for dysphagia: 14 endoscopic interventions for 5 patients (10%) and reoperation for 4 patients. Three patients (5%) in the EM group required reintervention for dysphagia: one endoscopic intervention each and no reoperations (p < 0.05). A total of 30 patients in the EM group were contacted in both 2001 (median follow-up period, 19 +/- 11 months) and 2005 (median follow-up period, 63 +/- 10 months). There was no significant change over time in dysphagia severity (2.6 +/- 1.9 vs 3.7 +/- 2.0; p = 0.19). For the treatment of achalasia, EM with Toupet fundoplication provides excellent durable dysphagia relief that is superior to SM with Dor fundoplication.

Energy extraction efficiency of a free electron laser (FEL) can be greatly increased using a tapered undulator and self-seeding. However, the extraction rate is limited by various effects that eventually lead to saturation of the peak intensity and power. To better understand these effects, we develop a model extending the Kroll-Morton-Rosenbluth, one-dimensional theory to include the physics of diffraction, optical guiding, and radially resolved particle trapping. The predictions of the model agree well with that of the GENESIS single-frequency numerical simulations. In particular, we discuss the evolution of the electron-radiation interaction along the tapered undulator and show that the decreasing of refractive guiding is the major cause of the efficiency reduction, particle detrapping, and then saturation of the radiation power. With this understanding, we develop a multidimensional optimization scheme based on GENESIS simulations to increase the energy extraction efficiency via an improved taper profile and variation in electron beam radius. We present optimization results for hard x-ray tapered FELs, and the dependence of the maximum extractable radiation power on various parameters of the initial electron beam, radiation field, and the undulator system. We also study the effect of the sideband growth in a tapered FEL. Such growth induces increased particle detrapping and thus decreased refractive guiding that together strongly limit the overall energy extraction efficiency.

In this paper we analyze the high gain, high efficiency tapered free-electron laser amplifier with a prebunched electron beam. Simple scaling laws are derived for the peak output power and extraction efficiency and verified using 1D simulations. These studies provide useful analytical expressions which highlight the benefits resulting from fine control of the initial conditions of the system, namely the initial electron beam bunching and input seed radiation. When time-dependent effects are included, the sideband instability is known to limit the radiation amplification due to particle detrapping. We discuss two different approaches to mitigate the sideband growth via 1-D time dependent simulations. We find that a more aggressive taper enabled by strong prebunching and a modulation of the resonance condition are both effective methods for suppressing the sideband instability growth rate.