Free-electron lasing with compact beam-driven plasma wakefield accelerator.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators1-4. The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL)5, a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations6,7. So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators8. This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications9.

Guiding of Charged Particle Beams in Curved Plasma-Discharge Capillaries.

We present a new approach that demonstrates the deflection and guiding of relativistic electron beams over curved paths by means of the magnetic field generated in a plasma-discharge capillary. We experimentally prove that the guiding is much less affected by the beam chromatic dispersion with respect to a conventional bending magnet and, with the support of numerical simulations, we show that it can even be made dispersionless by employing larger discharge currents. This proof-of-principle experiment extends the use of plasma-based devices, that revolutionized the field of particle accelerators enabling the generation of GeV beams in few centimeters. Compared to state-of-the-art technology based on conventional bending magnets and quadrupole lenses, these results provide a compact and affordable solution for the development of next-generation tabletop facilities.

Effect of different therapeutic strategies on olfactory outcomes in patients with chronic rhinosinusitis with nasal polyps: a systematic review.

INTRODUCTION: Olfactory impairment is one of the cardinal symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), yet the effect of the currently available therapeutic options on the recovery of the sense of smell is not well defined. The aim of this systematic review was to compile the evidence on the impact of medical, surgical, and biological therapies on the olfactory outcomes in patients with CRSwNP. METHODS: This review was conducted by two reviewers, according to the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines. The quality of evidence of all studies included in the qualitative synthesis was evaluated using the Critical Appraisal Skills Programme (CASP). RESULTS: Forty-four studies were included in the qualitative synthesis (assessing sinonasal surgery [n = 23], biologics [n =15], and conventional medical treatment [n = 6]); most had moderate-to-high methodological quality. Overall, significant improvements in the sense of smell were detected with all analyzed interventions measured by either an objective or a subjective tool (or both). However, most studies used different outcome measurements, hindering comparisons between interventions, and data on clinically relevant changes were missing. CONCLUSION: Oral corticosteroids, biologics and sinonasal surgery improve olfactory impairment associated with CRSwNP, but the high variability among existing studies does not allow accurate comparisons.

Stable Operation of a Free-Electron Laser Driven by a Plasma Accelerator.

The breakthrough provided by plasma-based accelerators enabled unprecedented accelerating fields by boosting electron beams to gigaelectronvolt energies within a few centimeters [1-4]. This, in turn, allows the realization of ultracompact light sources based on free-electron lasers (FELs) [5], as demonstrated by two pioneering experiments that reported the observation of self-amplified spontaneous emission (SASE) driven by plasma-accelerated beams [6,7]. However, the lack of stability and reproducibility due to the intrinsic nature of the SASE process (whose amplification starts from the shot noise of the electron beam) may hinder their effective implementation for user purposes. Here, we report a proof-of-principle experiment using plasma-accelerated beams to generate stable and reproducible FEL light seeded by an external laser. FEL radiation is emitted in the infrared range, showing the typical exponential growth of its energy over six consecutive undulators. Compared to SASE, the seeded FEL pulses have energies 2 orders of magnitude larger and stability that is 3 times higher.

Time-resolved study of nonlinear photoemission in radio-frequency photoinjectors.

Photoemission is one of the fundamental processes that describes the generation of charged particles from materials irradiated by photons. The continuous progress in the development of ultrashort lasers allows investigation into the dynamics of the process at the femtosecond timescale. Here we report about experimental measurements using two ultrashort ultraviolet laser pulses to temporally probe the electrons release from a copper cathode in a radio-frequency photoinjector. By changing their relative delay, we studied how the release mechanism is affected by two-photon photoemission when tens of GW/cm2 intensities are employed. We evaluated the limits it poses on the achievable beam brightness and analyzed the resulting emission yield in terms of the electronic temperature by modeling the cathode as a two-temperature system.

Time-resolved characterization of ultrafast electrons in intense laser and metallic-dielectric target interaction.

High-intensity ultrashort laser pulses interacting with thin solid targets are able to produce energetic ion beams by means of extremely large accelerating fields set by the energetic ejected electrons. The characterization of such electrons is thus important in view of a complete understanding of the acceleration process. Here, we present a complete temporal-resolved characterization of the fastest escaping hot electron component for different target materials and thicknesses, using temporal diagnostics based on electro-optical sampling with 100 fs temporal resolution. Experimental evidence of scaling laws for ultrafast electron beam parameters have been retrieved with respect to the impinging laser energy (0.4-4 J range) and to the target material, and an empirical law determining the beam parameters as a function of the target thickness is presented.

Ultrafast electron and proton bunches correlation in laser-solid matter experiments.

The interaction of an ultra-intense laser with a solid state target allows the production of multi-MeV proton and ion beams. This process is explained by the target normal sheath acceleration (TNSA) model, predicting the creation of an electric field on the target rear side, due to an unbalanced positive charge. This process is related to the emission of relativistic ultrafast electrons, occurring at an earlier time. In this work, we highlight the correlations between the ultrafast electron component and the protons by their simultaneous detection by means of an electro-optical sampling and a time-of-flight diagnostics, respectively, supported by numerical simulations showing an excellent agreement.

Longitudinal Phase-Space Manipulation with Beam-Driven Plasma Wakefields.

The development of compact accelerator facilities providing high-brightness beams is one of the most challenging tasks in the field of next-generation compact and cost affordable particle accelerators, to be used in many fields for industrial, medical, and research applications. The ability to shape the beam longitudinal phase space, in particular, plays a key role in achieving high-peak brightness. Here we present a new approach that allows us to tune the longitudinal phase space of a high-brightness beam by means of plasma wakefields. The electron beam passing through the plasma drives large wakefields that are used to manipulate the time-energy correlation of particles along the beam itself. We experimentally demonstrate that such a solution is highly tunable by simply adjusting the density of the plasma and can be used to imprint or remove any correlation onto the beam. This is a fundamental requirement when dealing with largely time-energy correlated beams coming from future plasma accelerators.

Focusing of High-Brightness Electron Beams with Active-Plasma Lenses.

Plasma-based technology promises a tremendous reduction in size of accelerators used for research, medical, and industrial applications, making it possible to develop tabletop machines accessible for a broader scientific community. By overcoming current limits of conventional accelerators and pushing particles to larger and larger energies, the availability of strong and tunable focusing optics is mandatory also because plasma-accelerated beams usually have large angular divergences. In this regard, active-plasma lenses represent a compact and affordable tool to generate radially symmetric magnetic fields several orders of magnitude larger than conventional quadrupoles and solenoids. However, it has been recently proved that the focusing can be highly nonlinear and induce a dramatic emittance growth. Here, we present experimental results showing how these nonlinearities can be minimized and lensing improved. These achievements represent a major breakthrough toward the miniaturization of next-generation focusing devices.

Physical performance in newly diagnosed hypothyroidism: a pilot study.

OBJECTIVE: Hypothyroidism is complicated by neuromuscular symptoms (myalgias, slowness of movements, and tiredness) and signs (easy fatigability and cramps), which may have a negative impact on general well-being and quality of life. In a pilot, prospective, controlled study, we investigated the features of muscle dysfunction in hypothyroidism by disease questionnaire, biochemical measures, and physical performance tests. MATERIALS AND METHODS: Fifty-seven consecutive patients with newly diagnosed hypothyroidism were enrolled, 27 subclinical (S-Hypo) and 30 overt (O-Hypo). A series of 30 euthyroid subjects, with similar demographic characteristics, served as controls. Patients were administered a short disease questionnaire and underwent laboratory exams and standardized physical tests, both at baseline and after restoration of biochemical euthyroidism. RESULTS: Compared to euthyroid controls, the O-Hypo group showed significantly higher prevalence of neuromuscular symptoms and significantly higher serum creatine phosphokinase (CPK) levels (p value < 0.0001). S-Hypo had slightly higher CPK levels and prevalence of neuromuscular symptoms than controls. Both S-Hypo and O-Hypo patients performed worse than controls in the six-minute walking test. Differences between patients and controls in handgrip strength test and timed chair standing test failed to reach statistical significance (although a trend was noticeable), possibly due to the small sample size. In O-Hypo, an inverse correlation was found between CPK levels and the handgrip strength test (p value < 0.001). Restoration of euthyroidism was associated with normalization of questionnaire responses, six-minute walking test, as well as serum CPK levels. CONCLUSION: In addition to neuromuscular symptoms, hypothyroidism is associated with abnormalities of physical performance. The six-minute walking test is the most valuable test to assess this aspect. In the pilot study, levothyroxine therapy could reverse muscle functional abnormalities.

Sub-picosecond snapshots of fast electrons from high intensity laser-matter interactions.

The interaction of a high-intensity short-pulse laser with thin solid targets produces electron jets that escape the target and positively charge it, leading to the formation of the electrostatic potential that in turn governs the ion acceleration. The typical timescale of such phenomena is on the sub-picosecond level. Here we show, for the first time, temporally-resolved measurements of the first released electrons that escaped from the target, so-called fast electrons. Their total charge, energy and temporal profile are provided by means of a diagnostics based on Electro-Optical Sampling with temporal resolution below 100 fs.

Prevalence of abdominal aortic aneurysms and its relation with cardiovascular risk stratification: protocol of the Risk of Cardiovascular diseases and abdominal aortic Aneurysm in Varese (RoCAV) population based study.

BACKGROUND: Recent meta-analyses suggested that screening program for abdominal aortic aneurysms (AAA) in 65-year old males is cost-effective at prevalence of about 1%. Since some events occur also in females and among the youngers, screening could be feasible among those at higher risk, such as smokers or individuals with a family history of AAA. The RoCAV (Risk of Cardiovascular diseases and abdominal aortic Aneurysms in Varese) Project is a population-based study aimed to evaluate AAA prevalence in Northern Italy in males over-65 years as well as among females and younger males, and to identify new markers for risk stratification by collecting a large set of CVD risk factors. The aims of the project are: (i) cross-sectional evaluation of AAA prevalence (ii); evaluation of standard CVD risk score as criteria for selecting subgroup at higher risk to be included in a screening program; (iii) identification of new risk markers and risk score algorithm for AAA and CVD risk stratification; (iv) cost-effective evaluation during the follow-up. METHODS: Males aged 50-75 years and females aged 60-75 years, resident in the city of Varese (Lombardy Region), were randomly selected from the civil registry. Among 5198 successfully invited, 3777 subjects accepted to participate and were finally recruited (participation rate 63.8%) from June 2013 to May 2016. Trained operators administered a computerized anamnestic questionnaire, measured anthropometric parameters (BMI, body circumferences, skinfolds), blood pressure, ankle-brachial index, pulse wave velocity and performed abdominal aortic ultrasound scan, ECG and spirometry. All methods were internationally validated. A blood sample was collected and stored in biobank. A follow-up will be carried out through linkage with electronic records. DISCUSSION: Participation rate and data quality assessment were as expected and will reasonably allow to reach the project aims. The expected impact in public health of the RoCAV project will be the potential implementation of a AAA screening program to the whole region as well as the formulation of new criteria for risk assessment of AAA and CVD.

Masked hypertension in newly diagnosed hypothyroidism: a pilot study.

PURPOSE: Masked hypertension (MH) is the association of normal office blood pressure (BP) with high ambulatory or home BP. This condition is associated with increased cardiovascular target organ damage, as true hypertension. Because the relation with hypothyroidism is controversial, we investigated it in a pilot longitudinal and controlled study. METHODS: We consecutively enrolled 64 newly diagnosed hypothyroid patients, 38 subclinical (s-HYPO), and 26 overt (o-HYPO). The control group consisted of 50 euthyroid subjects seen at outpatient clinics. All participants underwent office and 24-h ambulatory BP measurement. RESULTS: BP monitoring revealed a higher prevalence of MH both in s-HYPO (26.3 %) and in o-HYPO (15.4 %) than in euthyroid subjects (10 %, p = 0.05); true hypertension also was more frequent in o-HYPO (11.5 %) and s-HYPO (10.5 %) than in controls (8 %, p = 0.03). The odds ratio for hypertension versus normotension confirmed a significantly increased risk of MH in hypothyroid patients versus euthyroid subjects (3.29, 1.08-10.08; p = 0.02). In a subgroup of patients reevaluated after restoration of euthyroidism, an improvement of BP profile was observed, especially in s-HYPO subgroup, with a decreased prevalence of MH (from 25 to 10.7 %) and true hypertension (from 10.7 to 3.4 %). CONCLUSIONS: Hypothyroidism may be an important predictor of higher BP values, with an increased risk of MH. Because MH is a cardiovascular risk and can be reversed by thyroid hormone replacement, its presence should represent an indication for thyroid hormone replacement therapy also in patients with s-HYPO.

The phenotype of newly diagnosed Graves' disease in Italy in recent years is milder than in the past: results of a large observational longitudinal study.

OBJECTIVE: The Merseburg triad (hyperthyroidism, goiter, and orbitopathy) characterizes classical description of Graves' disease (GD). Aim of this observational, longitudinal study was to evaluate the current clinical features of newly diagnosed GD in Italy. MATERIALS AND METHODS: In two Northern Italy centers (Varese and Pavia), 283 consecutive patients (211 women, 72 men; mean age 47.4 years) with newly diagnosed GD were recruited in the years 2010-2014. Diagnosis was based on established criteria, and thyroid volume was assessed by ultrasonography. A clinical severity score (CSS) to assess the overall disease severity was developed by grading each component of the Merseburg triad. RESULTS: At diagnosis, 45 % of patients had no goiter, and 30 % had a small goiter. The proportion of goitrous patients was much lower than in two Italian studies performed 20-30 years ago. Hyperthyroidism was subclinical in 16 % and mild in 29 % of patients, and Graves' orbitopathy was present in 20 %, usually mild, and active in only 2.5 % of patients. Using the CSS, less than half (44 %) of the patients had severe GD, while 22 % had mild and 34 % moderate disease. CSS was associated with a significantly higher risk of poorly controlled hyperthyroidism at 6 months. CONCLUSIONS: In Italy, a relevant proportion of Graves' patients at diagnosis have mild to moderate GD; about half of them have no goiter, slightly less than one-fifth have subclinical hyperthyroidism, and only 20 % have GO. Thus, the clinical phenotype of GD is milder than in the past, possibly due to both earlier diagnosis and treatment, and improved iodine nutrition.

Analogical optical modeling of the asymmetric lateral coherence of betatron radiation.

By exploiting analogical optical modeling of the radiation emitted by ultrarelativistic electrons undergoing betatron oscillations, we demonstrate peculiar properties of the spatial coherence through an interferometric method reminiscent of the classical Young's double slit experiment. The expected effects due to the curved trajectory and the broadband emission are accurately reproduced. We show that by properly scaling the fundamental parameters for the wavelength, analogical optical modeling of betatron emission can be realized in many cases of broad interest. Applications to study the feasibility of future experiments and to the characterization of beam diagnostics tools are described.

Performance analysis of communication links based on VCSEL and silicon photonics technology for high-capacity data-intensive scenario.

To face the increased demand for bandwidth, cost-effectiveness and simplicity of future Ethernet data communications, a comparison between two different solutions based on directly-modulated VCSEL sources and Silicon Photonics technologies is carried out. Also by exploiting 4-PAM modulation, the transmission of 50-Gb/s and beyond capacity per channel is analyzed by means of BER performance. Applications for optical backplane, very short reach and in case of client-optics networks and intra and inter massive data centers communications (up to 10 km) are taken into account. A comparative analysis based on the power consumption is also proposed.

Measurement of power spectral density of broad-spectrum visible light with heterodyne near field scattering and its scalability to betatron radiation.

We exploit the speckle field generated by scattering from a colloidal suspension to access both spatial and temporal coherence properties of broadband radiation. By applying the Wiener-Khinchine theorem to the retrieved temporal coherence function, information about the emission spectrum of the source is obtained in good agreement with the results of a grating spectrometer. Experiments have been performed with visible light. We prove more generally that our approach can be considered as a tool for modeling a variety of cases. Here we discuss how to apply such diagnostics to broad-spectrum betatron radiation produced in the laser-driven wakefield accelerator under development at SPARC LAB facility in Frascati.

Two-Color Radiation Generated in a Seeded Free-Electron Laser with Two Electron Beams.

We present the experimental evidence of the generation of coherent and statistically stable two-color free-electron laser radiation obtained by seeding an electron beam double peaked in energy with a laser pulse single spiked in frequency. The radiation presents two neat spectral lines, with time delay, frequency separation, and relative intensity that can be accurately controlled. The analysis of the emitted radiation shows a temporal coherence and a shot-to-shot regularity in frequency significantly enhanced with respect to the self-amplified spontaneous emission.

Workplace drug testing on urine samples: evidence for improving efficacy of a first-level screening programme.

BACKGROUND: Previous reports revealed poor performance in identifying drugs of abuse users through first-level workplace drug testing (WDT), based on urine samples. In a cross-sectional study, we evaluated: (i) the effect of creatinine normalization of drug values from diluted urine samples (creatinine levels ≤ 20 mg/dL) on the prevalence of drug users; (ii) the independent procedure-related predictors of positivity and dilution. METHODS: Workers' urine samples were collected at the workplace or at our certified laboratory between 2008 and 2012. All samples were analysed for drugs of abuse by immuno-enzymatic method in our laboratory, according to the Italian WDT law. Detectable drugs of abuse concentrations lower than the positive cutoff values were normalized based on mean levels of urinary creatinine. Detectable concentrations of drugs were confirmed by GC/MS. Multivariate logistic regression was used to detect independent procedure-related predictors of positive and diluted urine samples. RESULTS: Of the 3080 urine samples screened, 51 (1.7%) were found positive for some drugs of abuse (26 cannabinoids and 16 cocaine) and 116 (3.8%) were diluted. Seventeen out of 23 diluted urine samples with detectable concentrations of cannabinoids or cocaine were found positive after urine creatinine normalization and GC/MS confirmed both negative and positive results. This increased the percentage of positivity for cannabinoids and cocaine from 1.35% to 2.09% (+55%, p=0.0005), which is closer to the expected prevalence of drug users based on Italian self-reported surveys. Collection of samples in the laboratory was an independent predictor of positivity (OR=2.33, 95%CI 1.27-4.28) and diluted urine sample (OR=1.65, 95%CI 1.04-2.61). CONCLUSIONS: Efficacy of first-level WDT could be improved by well-controlled pre-analytical procedures and urine creatinine normalization of detected concentrations of drugs of abuse.

Improving long-term prediction of first cardiovascular event: the contribution of family history of coronary heart disease and social status.

OBJECTIVE: The aim of this study is to assess whether family history of coronary heart disease (CHD) and education as proxy of social status improve long-term cardiovascular disease risk prediction in a low-incidence European population. METHODS: The 20-year risk of first coronary or ischemic stroke events was estimated using sex-specific Cox models in 3956 participants of three population-based surveys in northern Italy, aged 35-69 years and free of cardiovascular disease at enrollment. The additional contribution of education and positive family history of CHD was defined as change in discrimination and Net Reclassification Improvement (NRI) over the model including 7 traditional risk factors. RESULTS: Kaplan-Meier 20-year risk was 16.8% in men (254 events) and 6.4% in women (102 events). Low education (hazard ratio=1.35, 95%CI 0.98-1.85) and family history of CHD (1.55; 1.19-2.03) were associated with the endpoint in men, but not in women. In men, the addition of education and family history significantly improved discrimination by 1%; NRI was 6% (95%CI: 0.2%-15.2%), raising to 20% (0.5%-44%) in those at intermediate risk. NRI in women at intermediate risk was 7%. CONCLUSION: In low-incidence populations, family history of CHD and education, easily assessed in clinical practice, should be included in long-term cardiovascular disease risk scores, at least in men.