Textile microfibers in wild Antarctic whelk Neobuccinum eatoni (Smith, 1875) from Terra Nova Bay (Ross Sea, Antarctica).

Antarctica has been affected directly and indirectly by human pressure for more than two centuries and recently plastic pollution has been recognized as a further potential threat for its unique biodiversity. Global long-range transport as well as local input from anthropogenic activities are potential sources of plastic pollution in both terrestrial and marine Antarctic territories. The present study evaluated the presence of microplastics in specimens of the Antarctic whelk Neobuccinum eatoni, a key species in benthic communities of the Ross Sea, one of the largest marine protected areas worldwide. To this aim, a thermo-oxidative extraction method was applied for microplastic isolation and quantification, and polymer identification was performed by manual µ-FTIR spectroscopy. Textile (semi-)synthetic or composite microfibers (length range: 0.8-5.7 mm) were found in 27.3% of whelk specimens, suggesting a low risk of bioaccumulation along Antarctic benthic food webs in the Ross Sea. Their polymer composition (of polyethylene terephthalate and cellulose-polyamide composites) matched those of outdoor technical clothing in use by the personnel of the Italian "Mario Zucchelli" station near Terra Nova Bay in the Ross Sea. Such findings indicate that sewage from base stations may act as potential local sources of textile microplastic fibers in this remote environment. More in-depth monitoring studies aiming at defining the extent of microplastic contamination related to such sources in Antarctica are encouraged.

Is hip morphology a risk factor for developing hip osteoarthritis? A systematic review with meta-analysis.

OBJECTIVE: To appraise the highest evidence on hip morphology as a risk factor for developing hip osteoarthritis (OA). DESIGN: We searched for studies evaluating the association between radiological hip morphology parameters and the prevalence, incidence or progression of hip OA (based on different radiographic and clinical criteria) in the MEDLINE, EMBASE, Web of Science, Scopus, Cochrane Library and PEDro databases from inception until June 2020. Prospective and cross-sectional studies were separately evaluated. Data are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We included 9 prospective and 21 cross-sectional studies in the meta-analysis, and evaluated 42,831 hips from 25,898 individuals (mean age: 59 years). Prospective studies showed that, compared with control hips, hips with cam morphology (alpha angle >60°; OR = 2.52, 95% CI: 1.83 to 3.46, P < 0.001) or hip dysplasia (lateral center-edge angle (LCEA) <25°; OR = 2.38, 95% CI: 1.84 to 3.07, P < 0.001), but not hips with pincer morphology (LCEA >39°; OR = 1.08, 95% CI: 0.57 to 2.07, P = 0.810), were more likely to develop hip OA than hips without these morphologies. Cross-sectional studies showed a greater prevalence of pincer morphology (LCEA >39°, OR = 3.71, 95% CI: 2.98 to 4.61, P < 0.001) and acetabular retroversion (crossover sign; OR = 2.65, 95% CI: 1.17 to 6.03, P = 0.020) in hips with OA than in control hips. CONCLUSION: Cam morphology and hip dysplasia were consistently associated with the development of hip OA. Pincer morphology was associated with hip OA in cross-sectional but not in prospective studies. The heterogeneous quantification of pincer morphology on radiographs limits a clear conclusion on its association with hip OA.

Generation and Characterization of Intense Ultralow-Emittance Electron Beams for Compact X-Ray Free-Electron Lasers.

The transverse emittance of the electron beam is a fundamental parameter in linac-based x-ray free-electron lasers (FELs). We present results of emittance measurements carried out at SwissFEL, a compact x-ray FEL facility at the Paul Scherrer Institute in Switzerland, including a description of the novel high-resolution measurement techniques and the optimization procedure. We obtained slice emittance values at the undulator entrance down to 200 nm for an electron beam with a charge of 200 pC and an rms duration of 30-40 fs. Furthermore, we achieved slice emittances as low as 100 nm for 10 pC beams with few fs duration. These values set new standards for electron linear accelerators. The quality, verification, and control of our electron beams allowed us to generate high-power FEL radiation for a wavelength as short as 0.1 nm using an electron beam with an energy of only 6 GeV. The emittance values demonstrated at SwissFEL would allow producing hard x-ray FEL pulses with even lower-energy beams, thus paving the way for even more compact and cost-effective FEL facilities.

Passive Linearization of the Magnetic Bunch Compression Using Self-Induced Fields.

In linac-driven free-electron lasers, colliders, and energy recovery linacs, a common way to compress the electron bunch to kiloampere level is based upon the implementation of a magnetic dispersive element that converts particle energy deviation into a path-length difference. Nonlinearities of such a process are usually compensated by enabling a high harmonic rf structure properly tuned in amplitude and phase. This approach is however not straightforward, e.g., in C-band and X-band linacs. In this Letter we demonstrate that the longitudinal self-induced field excited by the electron beam itself is able to linearize the compression process without any use of high harmonic rf structure. The method is implemented at the FERMI linac, with the resulting high quality beam used to drive the seeded free-electron laser during user experiments.

Observation and Control of Laser-Enabled Auger Decay.

Single-photon laser-enabled Auger decay (spLEAD) is predicted theoretically [B. Cooper and V. Averbukh, Phys. Rev. Lett. 111, 083004 (2013)PRLTAO0031-900710.1103/PhysRevLett.111.083004] and here we report its first experimental observation in neon. Using coherent, bichromatic free-electron laser pulses, we detect the process and coherently control the angular distribution of the emitted electrons by varying the phase difference between the two laser fields. Since spLEAD is highly sensitive to electron correlation, this is a promising method for probing both correlation and ultrafast hole migration in more complex systems.

Time-Resolved Measurement of Interatomic Coulombic Decay Induced by Two-Photon Double Excitation of Ne_{2}.

The hitherto unexplored two-photon doubly excited states [Ne^{*}(2p^{-1}3s)]_{2} were experimentally identified using the seeded, fully coherent, intense extreme ultraviolet free-electron laser FERMI. These states undergo ultrafast interatomic Coulombic decay (ICD), which predominantly produces singly ionized dimers. In order to obtain the rate of ICD, the resulting yield of Ne_{2}^{+} ions was recorded as a function of delay between the extreme ultraviolet pump and UV probe laser pulses. The extracted lifetimes of the long-lived doubly excited states, 390(-130/+450) fs, and of the short-lived ones, less than 150 fs, are in good agreement with ab initio quantum mechanical calculations.

Epidemiology and cerebrovascular events related to cervical and intracranial arteries dissection: the experience of the city of Pisa.

Spontaneous dissection of cervical arteries (sCAD) is a major cause of ischemic stroke in young patients, with an incidence varying from 1.7 to 3/100,000/year for extracranial internal carotid artery (ICAD) and 1 to 1.9/100,000/year for extracranial vertebral artery (VAD). Reliable epidemiological data on stroke incidence related to sCAD are scarce in Italy. This study aims to evaluate the incidence, clinical features, and outcome of cerebrovascular events related to sCAD and spontaneous intracranial arteries dissections (sIAD) in the city of Pisa (Italy). We retrospectively analyzed consecutive patients admitted between December 1997 and June 2015 with a diagnosis of stroke, TIA, or Bernard-Horner syndrome due to acute cervical or intracranial artery dissection. Considering that our hospital collects presumptively all patients hospitalized with sCAD coming from the referral geographical area, data may provide a good approximation to real incidence of sCAD in our population. Clinical and radiological features, acute treatment and outcome were collected. Seventy-seven cases were included (mean age 48.1±10.4 years, range 23-77,72.7% males), 66 residents in the district of Pisa. Crude incidence rate of cerebrovascular events due to intra or extracranial dissection was 1.88/100,000/year. The incidence of ICAD was 0.80/100,000/year and 0.43/100,000/year for VAD. Stroke occurred in 76.6% of patients. VAD was more prone to cause ischemic stroke and present with cervical pain or focal signs (p < 0.01) than ICAD group, which had older age at onset. sIAD were more frequent in the posterior circle (p = 0.01) and more associated with ischemic lesions. A good outcome (mRS 0-2) was observed in 79% of patients. This is the first epidemiological attempt to investigate impact of sCAD and sIAD in Italy.

Slow Interatomic Coulombic Decay of Multiply Excited Neon Clusters.

Ne clusters (∼5000 atoms) were resonantly excited (2p→3s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate.

Investigation into local cell mechanics by atomic force microscopy mapping and optical tweezer vertical indentation.

Investigating the mechanical properties of cells could reveal a potential source of label-free markers of cancer progression, based on measurable viscoelastic parameters. The Young's modulus has proved to be the most thoroughly studied so far, however, even for the same cell type, the elastic modulus reported in different studies spans a wide range of values, mainly due to the application of different experimental conditions. This complicates the reliable use of elasticity for the mechanical phenotyping of cells. Here we combine two complementary techniques, atomic force microscopy (AFM) and optical tweezer microscopy (OTM), providing a comprehensive mechanical comparison of three human breast cell lines: normal myoepithelial (HBL-100), luminal breast cancer (MCF-7) and basal breast cancer (MDA-MB-231) cells. The elastic modulus was measured locally by AFM and OTM on single cells, using similar indentation approaches but different measurement parameters. Peak force tapping AFM was employed at nanonewton forces and high loading rates to draw a viscoelastic map of each cell and the results indicated that the region on top of the nucleus provided the most meaningful results. OTM was employed at those locations at piconewton forces and low loading rates, to measure the elastic modulus in a real elastic regime and rule out the contribution of viscous forces typical of AFM. When measured by either AFM or OTM, the cell lines' elasticity trend was similar for the aggressive MDA-MB-231 cells, which were found to be significantly softer than the other two cell types in both measurements. However, when comparing HBL-100 and MCF-7 cells, we found significant differences only when using OTM.

The FERMI free-electron lasers.

FERMI is a seeded free-electron laser (FEL) facility located at the Elettra laboratory in Trieste, Italy, and is now in user operation with its first FEL line, FEL-1, covering the wavelength range between 100 and 20 nm. The second FEL line, FEL-2, a high-gain harmonic generation double-stage cascade covering the wavelength range 20-4 nm, has also completed commissioning and the first user call has been recently opened. An overview of the typical operating modes of the facility is presented.

Experimental demonstration of enhanced self-amplified spontaneous emission by an optical klystron.

We report the first experimental evidence of enhancement of self-amplified spontaneous emission, due to the use of an optical klystron. In this free-electron laser scheme, a relativistic electron beam passes through two undulators, separated by a dispersive section. The latter converts the electron-beam energy modulation produced in the first undulator in density modulation, thus enhancing the free-electron laser gain. The experiment has been carried out at the FERMI facility in Trieste. Powerful radiation has been produced in the extreme ultraviolet range, with an intensity a few orders of magnitude larger than in pure self-amplified spontaneous emission mode. Data have been benchmarked with an existing theoretical model.

Multicolor High-Gain Free-Electron Laser Driven by Seeded Microbunching Instability.

Laser-heater systems are essential tools to control and optimize high-gain free-electron lasers (FELs) working in the x-ray wavelength range. Indeed, these systems induce a controllable increase of the energy spread of the electron bunch. The heating suppresses longitudinal microbunching instability which otherwise would limit the FEL performance. Here, we demonstrate that, through the action of the microbunching instability, a long-wavelength modulation of the electron beam induced by the laser heater at low energy can persist until the beam entrance into the undulators. This coherent longitudinal modulation is exploited to control the FEL spectral properties, in particular, multicolor extreme-ultraviolet FEL pulses can be generated through a frequency mixing of the modulations produced by the laser heater and the seed laser in the electron beam. We present an experimental demonstration of this novel configuration carried out at the FERMI FEL.

Comparative drug screening in NUT midline carcinoma.

BACKGROUND: The NUT midline carcinoma (NMC) is a rare but fatal cancer for which systematic testing of therapy options has never been performed. METHODS: On the basis of disease biology, we compared the efficacy of the CDK9 inhibitor flavopiridol (FP) with a panel of anticancer agents in NMC cell lines and mouse xenografts. RESULTS: In vitro anthracyclines, topoisomerase inhibitors, and microtubule poisons were among the most cytotoxic drug classes for NMC cells, while efficacy of the bromodomain inhibitor JQ1 varied considerably between lines carrying different BRD4 (bromodomain-containing protein 4)-NUT (nuclear protein in testis) translocations. Efficacy of FP was comparable to vincristine and doxorubicin, drugs that have been previously used in NMC patients. All three compounds showed significantly better activity than etoposide and vorinostat, agents that have also been used in NMC patients. Statins and antimetabolites demonstrated intermediate single-agent efficacy. In vivo, vincristine significantly inhibited tumour growth in two different NMC xenografts. Flavopiridol in vivo was significantly effective in one of the two NMC xenograft lines, demonstrating the biological heterogeneity of this disease. CONCLUSIONS: These results demonstrate that FP may be of benefit to a subset of patients with NMC, and warrant a continued emphasis on microtubule inhibitors, anthracyclines, and topoisomerase inhibitors as effective drug classes in this disease.

Impact of non-Gaussian electron energy heating upon the performance of a seeded free-electron laser.

Laser-heater systems have been demonstrated to be an important component for the accelerators that drive high gain free electron laser (FEL) facilities. These heater systems suppress longitudinal microbunching instabilities by inducing a small and controllable slice energy spread to the electron beam. For transversely uniform heating, the energy spread augmentation is characterized by a non-Gaussian distribution. In this Letter, we demonstrate experimentally that in addition to suppression of the microbunching instability, the laser heater-induced energy distribution can be preserved to the FEL undulator entrance, significantly impacting the performance of high-gain harmonic generation (HGHG) FELs, especially at soft x-ray wavelengths. In particular, we show that the FEL intensity has several local maxima as a function of the induced heating caused by the non-Gaussian energy distribution together with a strong enhancement of the power at high harmonics relative to that expected for an electron beam with an equivalent Gaussian energy spread at an undulator entrance. These results suggest that a single stage HGHG FEL can produce scientifically interesting power levels at harmonic numbers m ≥ 25 and with current seed laser technology could reach output photon energies above 100 eV or greater.

Experimental demonstration of electron longitudinal-phase-space linearization by shaping the photoinjector laser pulse.

Control of the electron-beam longitudinal-phase-space distribution is of crucial importance in a number of accelerator applications, such as linac-driven free-electron lasers, colliders and energy recovery linacs. Some longitudinal-phase-space features produced by nonlinear electron beam self- fields, such as a quadratic energy chirp introduced by geometric longitudinal wakefields in radio-frequency (rf) accelerator structures, cannot be compensated by ordinary tuning of the linac rf phases nor corrected by a single high harmonic accelerating cavity. In this Letter we report an experimental demonstration of the removal of the quadratic energy chirp by properly shaping the electron beam current at the photoinjector. Specifically, a longitudinal ramp in the current distribution at the cathode linearizes the longitudinal wakefields in the downstream linac, resulting in a flat electron current and energy distribution. We present longitudinal-phase-space measurements in this novel configuration compared to those typically obtained without longitudinal current shaping at the FERMI linac.

Magnetization and microstructure dynamics in Fe/MnAs/GaAs(001): Fe magnetization reversal by a femtosecond laser pulse.

Thin film magnetization reversal without applying external fields is an attractive perspective for applications in sensors and devices. One way to accomplish it is by fine-tuning the microstructure of a magnetic substrate via temperature control, as in the case of a thin Fe layer deposited on a MnAs/GaAs(001) template. This work reports a time-resolved resonant scattering study exploring the magnetic and structural properties of the Fe/MnAs system, using a 100 fs optical laser pulse to trigger local temperature variations and a 100 fs x-ray free-electron laser pulse to probe the induced magnetic and structural dynamics. The experiment provides direct evidence that a single optical laser pulse can reverse the Fe magnetization locally. It reveals that the time scale of the magnetization reversal is slower than that of the MnAs structural transformations triggered by the optical pulse, which take place after a few picoseconds already.

A method to generate perfusable physiologic-like vascular channels within a liver-on-chip model.

The human vasculature is essential in organs and tissues for the transport of nutrients, metabolic waste products, and the maintenance of homeostasis. The integration of vessels in in vitro organs-on-chip may, therefore, improve the similarity to the native organ microenvironment, ensuring proper physiological functions and reducing the gap between experimental research and clinical outcomes. This gap is particularly evident in drug testing and the use of vascularized models may provide more realistic insights into human responses to drugs in the pre-clinical phases of the drug development pipeline. In this context, different vascularized liver models have been developed to recapitulate the architecture of the hepatic sinusoid, exploiting either porous membranes or bioprinting techniques. In this work, we developed a method to generate perfusable vascular channels with a circular cross section within organs-on-chip without any interposing material between the parenchyma and the surrounding environment. Through this technique, vascularized liver sinusoid-on-chip systems with and without the inclusion of the space of Disse were designed and developed. The recapitulation of the Disse layer, therefore, a gap between hepatocytes and endothelial cells physiologically present in the native liver milieu, seems to enhance hepatic functionality (e.g., albumin production) compared to when hepatocytes are in close contact with endothelial cells. These findings pave the way to numerous further uses of microfluidic technologies coupled with vascularized tissue models (e.g., immune system perfusion) as well as the integration within multiorgan-on-chip settings.

Coherent light with tunable polarization from single-pass free-electron lasers.

Tunable polarization over a wide spectral range is a required feature of light sources employed to investigate the properties of local symmetry in matter. In this Letter, we provide the first experimental characterization of the polarization of the harmonic light produced by a free-electron laser and demonstrate a method to obtain free-electron laser harmonics with tunable polarization. Experimental results are successfully compared with theory. Our findings can be expected to have a deep impact on the design and realization of experiments requiring full control of light polarization.

[Organization and management of acute complete atrioventricular block: Results from a Multicenter National Survey]. / Organisation et gestion aiguë du bloc atrioventriculaire complet : résultats d'une enquête multicentrique nationale.

BACKGROUND: Complete atrioventricular block (AVB3) may be an urgent potentially lifethreatening situation. Our objective was to describe the routine management of AVB 3, with emphasis on the organizational aspects. METHODS: From September 2019 to November 2019, a prospective national survey including 28 questions was electronically sent to 100 physicians (Google Form). RESULTS: The answers were collected from 93 physicians (response rate 93%). Permanent pacemaker implantation during weekends and nights (after 8PM) is possible for 49% of the operators (<5 times a year), for 15% (>5 times a year), impossible for 36% of the operators. For AVB3 nonresponsive to isoproterenol occurring during the night, a temporary pacing lead (TPL) is implanted by: the on-site medical staff on-duty (27%), the on-call interventional cardiologist (21%), the on-call electrophysiologist (19%), a permanent pacemaker is implanted by the electrophysiologist (12%), the strategy is not standardized (15%). An externalized active fixation lead (AFL) for AVB3 has already been implanted by 50% of the operators. 80 (86%) have already observed a dislocation of the TPL, a cardiac perforation already occurred in 57 (61%), a groin hematoma in 35 (38%), and this technique was proscribed for 4% of the operators. CONCLUSION: Our survey shows important disparities in terms of management of AVB3 among the different centers. An externalized AFL with a reusable generator was used by half of the centers.