The Physics Beyond Colliders initiative is an exploratory study aimed at exploiting the full scientific potential of the CERN's accelerator complex and scientific infrastructures through projects ...complementary to the LHC and other possible future colliders. These projects will target fundamental physics questions in modern particle physics. This document presents the status of the proposals presented in the framework of the Beyond Standard Model physics working group, and explore their physics reach and the impact that CERN could have in the next 10-20 years on the international landscape.
We investigate experimentally the emergence of collective motion in the bulk of an active suspension of Escherichia coli bacteria. When increasing the concentration from a dilute to a semi-dilute ...regime, we observe a continuous crossover from a dynamical cluster regime to a regime of 'bio-turbulence' convection patterns. We measure a length scale characterizing the collective motion as a function of the bacteria concentration. For bacteria fully supplied with oxygen, the increase of the correlation length is almost linear with concentration and at the largest concentrations tested, the correlation length could be as large as 24 bacterial body sizes (or 7-8 when including the flagella bundle). In contrast, under conditions of oxygen shortage the correlation length saturates at a value of around 7 body lengths.
This document constitutes an excerpt of the Technical Design Report for the second stage of the "Any Light Particle Search" (ALPS-II) at DESY as submitted to the DESY PRC in August 2012 and reviewed ...in November 2012. ALPS-II is a "Light Shining through a Wall" experiment which searches for photon oscillations into weakly interacting sub-eV particles. These are often predicted by extensions of the Standard Model and motivated by astrophysical phenomena. The first phases of the ALPS-II project were approved by the DESY management on 21 February, 2013.
Background Sepsis-3 definition uses SOFA score to discriminate sepsis from uncomplicated infection, replacing SIRS criteria that were criticized for being inaccurate. Eligibility of sepsis-3 criteria ...for sepsis diagnosis and the applied validation methodology using mortality as endpoint are topic of ongoing debate. We assessed the impact of different criteria on sepsis diagnosis in our ICU and devised a mathematical approach for mortality-based validation of sepsis criteria. As infectious status is often unclear at clinical deterioration, we integrated non-infected patients into analysis. Methods Suspected infection, SOFA and SIRS were captured for an ICU cohort of a university center over one year. For raw scores (SIRS/SOFA) and sepsis criteria (SIRSgreater than or equal to2/SOFAgreater than or equal to2/SOFA_changegreater than or equal to2) frequencies and associations with in-hospital mortality were assessed. Using a mathematical approach, we estimated the correlation between sepsis and in-hospital mortality serving as reference for evaluation of observed mortality correlations of sepsis criteria. Results Of 791 patients, 369 (47%) were infected and 422 (53%) non-infected, with an in-hospital mortality of 39% and 15%. SIRSgreater than or equal to2 indicated sepsis in 90% of infected patients, SOFAgreater than or equal to2 in 99% and SOFA_changegreater than or equal to2 in 77%. In non-infected patients, SIRS, SOFA and SOFA_change were greater than or equal to2 in 78%, 88% and 58%. In AUROC analyses neither SOFA nor SIRS displayed superior mortality discrimination in infected compared to non-infected patients. The mathematically estimated correlation of sepsis and in-hospital mortality was 0.10 in infected and 0 in non-infected patients. Among sepsis criteria, solely SIRSgreater than or equal to2 agreed with expected correlations in both subgroups (infected: r = 0.19; non-infected: r = 0.02). Conclusions SOFAgreater than or equal to2 yielded a more liberal sepsis diagnosis than SIRSgreater than or equal to2. None of the criteria showed an infection specific occurrence that would be essential for reliable sepsis detection. However, SIRSgreater than or equal to2 matched the mortality association pattern of a valid sepsis criterion, whereas SOFA-based criteria did not. With this study, we establish a mathematical approach to mortality-based evaluation of sepsis criteria.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations ...are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.
A common final pathway of pathogenetic mechanisms in septic organ dysfunction and death is a lack or non-utilization of oxygen. Plasma concentrations of lactate serve as surrogates for the ...oxygen-deficiency-induced imbalance between energy supply and demand. As S-adenosylhomocysteine (SAH) was shown to reflect tissue hypoxia, we compared the ability of SAH versus lactate to predict the progression of inflammatory and septic disease to septic organ dysfunction and death. Using univariate and multiple logistic regression, we found that SAH but not lactate, taken upon patients’ inclusion in the study close to ICU admission, significantly and independently contributed to the prediction of disease progression and death. Due to the stronger increase in SAH in relation to S-adenosylmethionine (SAM), the ratio of SAM to SAH, representing methylation potential, was significantly decreased in patients with septic organ dysfunction and non-survivors compared with SIRS/sepsis patients (2.8 (IQR 2.3–3.9) vs. 8.8 (4.9–13.8); p = 0.003) or survivors (4.9 (2.8–9.5) vs. 8.9 (5.1–14.3); p = 0.026), respectively. Thus, SAH appears to be a better contributor to the prediction of septic organ dysfunction and death than lactate in critically ill patients. As SAH is a potent inhibitor of SAM-dependent methyltransferases involved in numerous vital biochemical processes, the impairment of the SAM-to-SAH ratio in severely critically ill septic patients and non-survivors warrants further studies on the pathogenetic role of SAH in septic multiple organ failure.
The pathological processes by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that make the virus a major threat to global health are insufficiently understood. Inefficient ...viral clearance at any stage is a hallmark of coronavirus disease 2019 (COVID-19). Disease severity is associated with increases in peripheral blood cytokines among which interleukin 10 (IL-10) increases particularly early and independent of patient age, which is not seen in active SARS-CoV infection. Here, we consider the known multi-faceted immune regulatory role of IL-10, both in protecting the lung from injury and in defense against infections, as well as its potential cellular source. While the absence of an IL-10 response in SARS is thought to contribute to early deterioration, we suspect IL-10 to protect the lung from early immune-mediated damage and to interfere with viral clearance in COVID-19. This may further both viral spread and poor outcome in many high-risk patients. Identifying the features of the viral genotype, which specifically underlie the different IL-10 dynamics as an etiological endotype and the different viral load kinetics and outcomes as clinical phenotype, may unveil a new immune evasive strategy of SARS-CoV-2.
With the ability to create customizable products tailored to individual patients, the use of 3D printed medical devices has rapidly increased in recent years. Despite such interest in these ...materials, a risk assessment based on the material characterization of final device extracts-as per regulatory guidance-has not yet been completed, even though the printing process may potentially impact the leachability of polymer components. To further our understanding of the chemical impact of 3D printed medical devices, this study investigated the extractable profiles of four different materials, including a PLA polymer advertised as "FDA-approved". The fusion deposition modeling (FDM) printing process created distinct chemical and physical signatures in the extracts of certain materials. The application of an annealing procedure to printed devices led to a substantial decrease in extractable components by as much as a factor of 50. In addition, the use of a brass printing nozzle led to an increase in the amount of Pb detected in 3D printed device extracts. The data generated provides valuable information that can be used to help assess extractable risks of 3D printed medical devices, assist with future 3D printing designs, and may provide insight for agencies tasked with governing 3D printed medical device regulations.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Statistical network analyses have become popular in many scientific disciplines, where an important task is to test for differences between two networks. We describe an overall framework for ...differential network testing procedures that vary regarding (1) the network estimation method, typically based on specific concepts of association, and (2) the network characteristic employed to measure the difference. Using permutation-based tests, our approach is general and applicable to various overall, node-specific or edge-specific network difference characteristics. The methods are implemented in our freely available R software package DNT, along with an R Shiny application. In a study in intensive care medicine, we compare networks based on parameters representing main organ systems to evaluate the prognosis of critically ill patients in the intensive care unit (ICU), using data from the surgical ICU of the University Medical Centre Mannheim, Germany. We specifically consider both cross-sectional comparisons between a non-survivor and a survivor group and longitudinal comparisons at two clinically relevant time points during the ICU stay: first, at admission, and second, at an event stage prior to death in non-survivors or a matching time point in survivors. The non-survivor and the survivor networks do not significantly differ at the admission stage. However, the organ system interactions of the survivors then stabilize at the event stage, revealing significantly more network edges, whereas those of the non-survivors do not. In particular, the liver appears to play a central role for the observed increased connectivity in the survivor network at the event stage.
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