The soft X-ray monochromator at the SASE3 beamline of the European XFEL: from design to operation.

The SASE3 soft X-ray beamline at the European XFEL has been designed and built to provide experiments with a pink or monochromatic beam in the photon energy range 250-3000 eV. Here, the focus is monochromatic operation of the SASE3 beamline, and the design and performance of the SASE3 grating monochromator are reported. The unique capability of a free-electron laser source to produce short femtosecond pulses of a high degree of coherence challenges the monochromator design by demanding control of both photon energy and temporal resolution. The aim to transport close to transform-limited pulses poses very high demands on the optics quality, in particular on the grating. The current realization of the SASE3 monochromator is discussed in comparison with optimal design performance. At present, the monochromator operates with two gratings: the low-resolution grating is optimized for time-resolved experiments and allows for moderate resolving power of about 2000-5000 along with pulse stretching of a few to a few tens of femtoseconds RMS, and the high-resolution grating reaches a resolving power of 10 000 at the cost of larger pulse stretching.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.

Thromboelastography clot strength profiles and effect of systemic anticoagulation in COVID-19 acute respiratory distress syndrome: a prospective, observational study.

OBJECTIVE: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection may yield a hypercoagulable state with fibrinolysis impairment. We conducted a single-center observational study with the aim of analyzing the coagulation patterns of intensive care unit (ICU) COVID-19 patients with both standard laboratory and viscoelastic tests. The presence of coagulopathy at the onset of the infection and after seven days of systemic anticoagulant therapy was investigated. PATIENTS AND METHODS: Forty consecutive SARS-CoV-2 patients, admitted to the ICU of a University hospital in Italy between 29th February and 30th March 2020 were enrolled in the study, providing they fulfilled the acute respiratory distress syndrome criteria. They received full-dose anticoagulation, including Enoxaparin 0.5 mg·kg-1 subcutaneously twice a day, unfractionated Heparin 7500 units subcutaneously three times daily, or low-intensity Heparin infusion. Thromboelastographic (TEG) and laboratory parameters were measured at admission and after seven days. RESULTS: At baseline, patients showed elevated fibrinogen activity [rTEG-Ang 80.5° (78.7 to 81.5); TEG-ACT 78.5 sec (69.2 to 87.9)] and an increase in the maximum amplitude of clot strength [FF-MA 42.2 mm (30.9 to 49.2)]. No alterations in time of the enzymatic phase of coagulation [CKH-K and CKH-R, 1.1 min (0.85 to 1.3) and 6.6 min (5.2 to 7.5), respectively] were observed. Absent lysis of the clot at 30 minutes (LY30) was observed in all the studied population. Standard coagulation parameters were within the physiological range: [INR 1.09 (1.01 to 1.20), aPTT 34.5 sec (29.7 to 42.2), antithrombin 97.5% (89.5 to 115)]. However, plasma fibrinogen [512.5 mg·dl-1 (303.5 to 605)], and D-dimer levels [1752.5 ng·ml-1 (698.5 to 4434.5)], were persistently increased above the reference range. After seven days of full-dose anticoagulation, average TEG parameters were not different from baseline (rTEG-Ang p = 0.13, TEG-ACT p = 0.58, FF-MA p = 0.24, CK-R p = 0.19, CKH-R p  = 0.35), and a persistent increase in white blood cell count, platelet count and D-dimer was observed (white blood cell count p < 0.01, neutrophil count p = 0.02, lymphocyte count p < 0.01, platelet count p = 0.13 < 0.01, D-dimer levels p= 0.02). CONCLUSIONS: SARS-CoV-2 patients with acute respiratory distress syndrome show elevated fibrinogen activity, high D-dimer levels and maximum amplitude of clot strength. Platelet count, fibrinogen, and standard coagulation tests do not indicate a disseminated intravascular coagulation. At seven days, thromboelastographic abnormalities persist despite full-dose anticoagulation.

Time- and momentum-resolved photoemission studies using time-of-flight momentum microscopy at a free-electron laser.

Time-resolved photoemission with ultrafast pump and probe pulses is an emerging technique with wide application potential. Real-time recording of nonequilibrium electronic processes, transient states in chemical reactions, or the interplay of electronic and structural dynamics offers fascinating opportunities for future research. Combining valence-band and core-level spectroscopy with photoelectron diffraction for electronic, chemical, and structural analyses requires few 10 fs soft X-ray pulses with some 10 meV spectral resolution, which are currently available at high repetition rate free-electron lasers. We have constructed and optimized a versatile setup commissioned at FLASH/PG2 that combines free-electron laser capabilities together with a multidimensional recording scheme for photoemission studies. We use a full-field imaging momentum microscope with time-of-flight energy recording as the detector for mapping of 3D band structures in (kx, ky, E) parameter space with unprecedented efficiency. Our instrument can image full surface Brillouin zones with up to 7 Å-1 diameter in a binding-energy range of several eV, resolving about 2.5 × 105 data voxels simultaneously. Using the ultrafast excited state dynamics in the van der Waals semiconductor WSe2 measured at photon energies of 36.5 eV and 109.5 eV, we demonstrate an experimental energy resolution of 130 meV, a momentum resolution of 0.06 Å-1, and a system response function of 150 fs.

The contribution of the TIPE (Test di Induzione PsicoErotica: PsychoErotic Induction Test) to the assessment of erotic fantasies in subjects affected by gender dysphoria: a case series.

Research into sexual aspects poses a fascinating challenge that is highly cogent to clinical profiling disciplines, but also constitutes a more 'narrative and culturally oriented' approach to medicine and psychology. Assessments of subjects affected by gender dysphoria and their internal, relational and sexual world is a still more complex task, since these are very distressing and tormented issues for the subjects under study. Psychodiagnostics can be an important element in the various investigative, evaluative and therapeutic pathways. The authors have focused attention on the TIPE (Test di Induzione PsicoErotica: PsychoErotic Induction Test), an Italian projective psychodiagnostic tool that is used to explore the psychoerotic fantasies of subjects affected by gender dysphoria. The TIPE tests protocols of two samples of subjects have been examined. They projected particularly rich narrative aspects of the subjects' psychoerotic imaginary world. The first sample, a clinical series, consisted of a total of eleven subjects, nine men and two women, mean age 43 years, who were undergoing assessment, firstly psychotherapeutic and then medicolegal, for sex rectification purposes; the second sample, the controls, consisted of fourteen subjects, nine men and five women, mean age 28 years, all heterosexual and with a problem-free history of sexual identity.

Acute HEV hepatitis: clinical and laboratory diagnosis.

OBJECTIVE: Hepatitis E Virus (HEV) is probably the most common cause of acute hepatitis worldwide. It has been regarded for a long time as a disease limited to developing countries. Recently, the refinement of diagnostic techniques, on the one hand, and migratory flows, on the other hand, have also led to the identification of an increased number of HEV infections in industrialized countries. Four HEV genotypes have been identified across the world, with different epidemiological burdens and a wide range of clinical presentations. Here, we report a case series of acute HEV hepatitis observed in the last three years in our hospital. PATIENTS AND METHODS: We performed a search for HEV IgM and IgG in all subjects admitted for acute hepatitis without evidence of other possible infectious, toxic or metabolic causes of liver damage. In subjects with HEV IgM positivity, the search for HEV-RNA was performed. RESULTS: We diagnosed eight acute HEV infections: 2 epidemic and 6 sporadic forms. HEV-RNA was detected in serum in 2 cases. CONCLUSIONS: HEV infection appears to be a cause of acute hepatitis that we must keep in mind even in developed countries.

Real-Time Elucidation of Catalytic Pathways in CO Hydrogenation on Ru.

The direct elucidation of the reaction pathways in heterogeneous catalysis has been challenging due to the short-lived nature of reaction intermediates. Here, we directly measured on ultrafast time scales the initial hydrogenation steps of adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction in syngas and CO2 reforming processes. We initiated the hydrogenation of CO with an ultrafast laser temperature jump and probed transient changes in the electronic structure using real-time X-ray spectroscopy. In combination with theoretical simulations, we verified the formation of CHO during CO hydrogenation.

Strong Influence of Coadsorbate Interaction on CO Desorption Dynamics on Ru(0001) Probed by Ultrafast X-Ray Spectroscopy and Ab Initio Simulations.

We show that coadsorbed oxygen atoms have a dramatic influence on the CO desorption dynamics from Ru(0001). In contrast to the precursor-mediated desorption mechanism on Ru(0001), the presence of surface oxygen modifies the electronic structure of Ru atoms such that CO desorption occurs predominantly via the direct pathway. This phenomenon is directly observed in an ultrafast pump-probe experiment using a soft x-ray free-electron laser to monitor the dynamic evolution of the valence electronic structure of the surface species. This is supported with the potential of mean force along the CO desorption path obtained from density-functional theory calculations. Charge density distribution and frozen-orbital analysis suggest that the oxygen-induced reduction of the Pauli repulsion, and consequent increase of the dative interaction between the CO 5σ and the charged Ru atom, is the electronic origin of the distinct desorption dynamics. Ab initio molecular dynamics simulations of CO desorption from Ru(0001) and oxygen-coadsorbed Ru(0001) provide further insights into the surface bond-breaking process.

Surface chemistry. Probing the transition state region in catalytic CO oxidation on Ru.

Femtosecond x-ray laser pulses are used to probe the carbon monoxide (CO) oxidation reaction on ruthenium (Ru) initiated by an optical laser pulse. On a time scale of a few hundred femtoseconds, the optical laser pulse excites motions of CO and oxygen (O) on the surface, allowing the reactants to collide, and, with a transient close to a picosecond (ps), new electronic states appear in the O K-edge x-ray absorption spectrum. Density functional theory calculations indicate that these result from changes in the adsorption site and bond formation between CO and O with a distribution of OC-O bond lengths close to the transition state (TS). After 1 ps, 10% of the CO populate the TS region, which is consistent with predictions based on a quantum oscillator model.

Structure and energetics of azobenzene on Ag(111): benchmarking semiempirical dispersion correction approaches.

We employ normal-incidence x-ray standing wave and temperature programed desorption spectroscopy to derive the adsorption geometry and energetics of the prototypical molecular switch azobenzene at Ag(111). This allows us to assess the accuracy of semiempirical correction schemes as a computationally efficient means to overcome the deficiency of semilocal density-functional theory with respect to long-range van der Waals (vdW) interactions. The obtained agreement underscores the significant improvement provided by the account of vdW interactions, with remaining differences mainly attributed to the neglect of electronic screening at the metallic surface.

Diurnal and nocturnal shifts do not influence non-invasive ventilation outcome.

AIM: The aim of this study was to assess if diurnal or nocturnal shifts were independent risk factors for non-invasive ventilation (NIV) failure. METHODS: This was an observational study carried out on 18 patients of the general Intensive Care Unit in Rome. A total number of 189 consecutive patients needing mechanical ventilation for respiratory failure were prospectively enrolled: 82 were treated with NIV as a first line intervention. Of the 107 patients who were initially intubated, 59 patients were extubated; once extubation failed they were treated with NIV. NIV failure was assessed during both the day (between 7 am and 10 pm) and night shifts (between 10 pm and 7 am). RESULTS: Of the 141 total patients who received NIV, 51 experienced failure during the day shifts and 18 during the night shifts. No difference in the median day and night shift TISS-28 values were observed in any patients who failed NIV during both day and night shifts. Causes of NIV failure were similar during both diurnal and nocturnal shifts. The inability to correct gas exchanges was the main reason for failure. CONCLUSION: In a center with NIV expertise, notwithstanding nurse understaffing, diurnal and nocturnal shifts did not affect the rate of NIV failure.

The 2008 international guidelines for management of severe sepsis and septic shock: merits and weaknesses.

The Guidelines are intended to provide standard guidance for the care of patients by grouping evidence-based interventions into bundles that can be easily used by clinicians to improve patient outcome. The 2008 International guidelines for management of severe sepsis and septic shock is a large and extraordinary update of the literature offered by current leaders in the field. Unfortunately, as a consensus of experts, most of whom expressed their opinions by voting, these guidelines do not always represent the state of the art. Furthermore, they can change if new participants take part in the process. By considering the merits and weaknesses of practice guidelines, we conclude that guidelines cannot replace a physician's judgments, but rather should be a starting point for more robust and proficient scientific evidence.

Efficacy and safety of continuous intravenous infusion of remifentanil in preterm infants undergoing laser therapy in retinopathy of prematurity: clinical experience.

BACKGROUND: Preterm infants often require surgery. As experimental evidence suggests that premature infants may experience pain and this could even result in fatal complications, the anaesthesiologist must face problems related to lowbirth weight, high risk of hypothermia, concomitant pulmonary disease and metabolic and receptor immaturity. Recently remifentanil has been considered an optimal analgesic drug in a preterm infant undergoing mechanical ventilation and frequent surgical manoeuvres, but no clinical studies have been reported in the literature. The aim of our study was to evaluate the efficacy of a continuous intravenous infusion of remifentanil in premature infants undergoing laser therapy for retinopathy of prematurity (ROP). METHODS: Six premature infants with ROP were scheduled for laser therapy. The procedure was performed in the neonatal intensive care unit. Transcutaneous carbon dioxide, pulse oximetry, respiratory rate, ECG and noninvasive blood pressure were continuously monitored. Infusion of remifentanil started with a dose of 0.75-1 microg x kg-1x min-1, 1 h before surgery. A midazolam bolus dose (0.20 mg x kg-1) was administered and the remifentanil infusion was increased to 3-5 microg x kg-1x min-1 taking into account haemodynamic and respiratory changes or spontaneous movements. RESULTS: Increased dosage was necessary only for 10 min during the procedure. No changes in temperature and ventilatory settings were observed and after 2 h from the surgical procedure the preterm infants were back to their preoperative status. CONCLUSIONS: A continuous infusion of remifentanil allowed optimal control of surgical stress and a return to preoperative status and ventilatory settings without side-effects.

Using environmental stressor information to predict the ecological status of Maryland non-tidal streams as measured by biological indicators.

In Maryland. U.S., an interim framework has recently been developed for using biologically based thresholds, or 'biocriteria', to assess the health of nontidal streams statewide at watershed scales. The evaluation of impairment is based on indices of biological integrity from the Maryland Biological Stream Survey (MBSS). We applied logistic regression to quantify how the biotic integrity of streams at a local scale is affected by cumulative effects resulting from catchment land uses, point sources, and nearby transmission line rights-of-way. Indicators for land use were developed from the remote sensing National Land Cover Data and applied at different scales. We determined that the risk of local impairment in nontidal streams rapidly increases with increased urban land use in the catchment area. The average likelihood of failing biocriteria doubled with every 10% points increment in urban land, thus an increase in urban land use from 0 to 20% quadruples the risk of impairment. For the basins evaluated in this study, catchments with more than 40-50% urban land use had greater than 80% probability of failing biocriteria, on average. Inclusion of rights-of-way and point sources in the model did not significantly improve the fit for this data set, most likely because of their low numbers. The overall results indicate that our predictive modeling approach can help pinpoint stream ecosystems experiencing or vulnerable to degradation.

Sedation in the Intensive Care Unit. The basis of the problem.

The authors briefly discuss the advantages and limits of sedation in critically ill patients. They also focus the importance of an individualized sedative approach which provides pain relief and modulates stress response, allowing patients to be easily arousable and cooperative as necessary.

[Acute respiratory failure in organ transplantation and immunodepressed patients]. / Insufficienza respiratoria acuta nel paziente immunodepresso e sottoposto a trapianto d'organo.

Recently, noninvasive ventilation (NIV) has been introduced as a new and alternative ventilatory method. The efficacy of NIV has been reported in immunosuppressed patients, with the decrease in drawbacks related to mechanical ventilation by endotracheal intubation. The authors propose an up-date on the use of NIV in transplanted patients.

De-escalation antimicrobial chemotherapy in critically III patients: pros and cons.

In spite of advances in critical care, nosocomial infections still have a considerable impact on Intensive Care Unit (ICU) and hospital length of stay, mortality and costs. Several authors suggest that antibiotic therapy should be instituted as soon as sepsis is suspected in critically patients. Over the last two decades the rates of occurrence for pathogens have significantly changed under selective pressure from broad-spectrum antimicrobial therapy. Shifts from predominance of gram-negative to gram-positive organisms and outbreaks of resistant pathogens address the need for appropriate empirical regimens. Agents such as ceftazidime, imipenem and, more recently, meropenem and tazobactam have been used successfully as monotherapy. Two different clinical trials have reported that meropenem monotherapy is significantly more effective than ceftazidime-based therapy. Because of the outbreak of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, some investigators suggest adding a glycopeptide to beta-lactamase inhibitor and carbapenem as initial empirical therapy. Such a regimen should be administered before definitive proof of infections and until the results of microbial investigation are available (de-escalation antimicrobial chemotherapy). On the other hand, several authors do not recommend glycopeptide administration in an attempt to limit nosocomial outbreaks of vancomycin-resistant enterococci (VRE) and staphylococci (VRS) and to avoid secondary drawbacks, such as nephrotoxicity and ototoxicity. De-escalation antimicrobial chemotherapy should be tailored to critically ill patients according to their clinical status, severity of illness and suspicion of sepsis or nosocomial pneumonia.

Elevated alanine aminotransferase in blood donors: role of different factors and multiple viral infections.

Many different aetiological agents stimulate alanine aminotransferase (ALT) production. Viral markers and other aetiologies were investigated in 2166 individuals, randomly selected from 10,000 consecutive blood donors. Elevation of ALT was found in 10.8% of subjects. Grouping donors according to ALT level and correlating with, respectively, hepatitis B core antibody (HBcAb), cytomegalovirus antibody alone, or associated with HBcAb, showed similar findings (high ALT 11.1%, normal 11.6%; high 85.4%, normal 81.4%; high 10.2%, normal 11.0%, respectively). Hepatitis C virus (HCV) antibody was found to be significantly associated with elevated ALT levels (high 1.7%, normal 0.26%). Other causes of ALT elevation were alcohol abuse (17%), obesity (25%) and dyslipidaemia (38%), but in 11% there was no obvious aetiology. Although HCV is a rare cause of elevated ALT in blood donors, it seems to be the only virus, among those tested, to account for liver damage. This may be due to the non-protective role of HCV antibody, the low specificity of ALT, or the pathogenic role of uninvestigated viruses.