OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

An integrated ultra-high vacuum apparatus for growth and in situ characterization of complex materials.

Here, we present an integrated ultra-high vacuum apparatus-named MBE-Cluster -dedicated to the growth and in situ structural, spectroscopic, and magnetic characterization of complex materials. Molecular Beam Epitaxy (MBE) growth of metal oxides, e.g., manganites, and deposition of the patterned metallic layers can be fabricated and in situ characterized by reflection high-energy electron diffraction, low-energy electron diffraction, Auger electron spectroscopy, x-ray photoemission spectroscopy, and azimuthal longitudinal magneto-optic Kerr effect. The temperature can be controlled in the range from 5 K to 580 K, with the possibility of application of magnetic fields H up to ±7 kOe and electric fields E for voltages up to ±500 V. The MBE-Cluster operates for in-house research as well as user facility in combination with the APE beamlines at Sincrotrone-Trieste and the high harmonic generator facility for time-resolved spectroscopy.

A reaction cell for ambient pressure soft x-ray absorption spectroscopy.

We present a new experimental setup for performing X-ray Absorption Spectroscopy (XAS) in the soft X-ray range at ambient pressure. The ambient pressure XAS setup is fully compatible with the ultra high vacuum environment of a synchrotron radiation spectroscopy beamline end station by means of ultrathin Si3N4 membranes acting as windows for the X-ray beam and seal of the atmospheric sample environment. The XAS detection is performed in total electron yield (TEY) mode by probing the drain current from the sample with a picoammeter. The high signal/noise ratio achievable in the TEY mode, combined with a continuous scanning of the X-ray energies, makes it possible recording XAS spectra in a few seconds. The first results show the performance of this setup to record fast XAS spectra from sample surfaces exposed at atmospheric pressure, even in the case of highly insulating samples. The use of a permanent magnet inside the reaction cell enables the measurement of X-ray magnetic circular dichroism at ambient pressure.

Establishment of an Italian chronic migraine database: a multicenter pilot study.

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments' responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database-shortly including many other Italian headache centers-will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

Spectroscopic identification of the chemical interplay between defects and dopants in Al-doped ZnO.

The conduction and optoelectronic properties of transparent conductive oxides can be largely modified by intentional inclusion of dopants over a very large range of concentrations. However, the simultaneous presence of structural defects results in an unpredictable complexity that prevents a clear identification of chemical and structural properties of the final samples. By exploiting the unique chemical sensitivity of Hard X-ray Photoelectron Spectra and Near Edge X-ray Absorption Fine Structure in combination with Density Functional Theory, we determine the contribution to the spectroscopic response of defects in Al-doped ZnO films. Satellite peaks in O1s and modifications at the O K-edge allow the determination of the presence of H embedded in ZnO and the very low concentration of Zn vacancies and O interstitials in undoped ZnO. Contributions coming from substitutional and (above the solubility limit) interstitial Al atoms have been clearly identified and have been related to changes in the oxide stoichiometry and increased oxygen coordination, together with small lattice distortions. In this way defects and doping in oxide films can be controlled, in order to tune their properties and improve their performances.

Performance of photoelectron spin polarimeters with continuous and pulsed sources: from storage rings to free electron lasers.

In this work the experimental uncertainties concerning electron spin polarization (SP) under various realistic measurement conditions are theoretically derived. The accuracy of the evaluation of the SP of the photoelectron current is analysed as a function of the detector parameters and specifications, as well as of the characteristics of the photoexcitation sources. In particular, the different behaviour of single counter or twin counter detectors when the intensity fluctuations of the source are considered have been addressed, leading to a new definition of the SP detector performance. The widely used parameter called the figure of merit is shown to be inadequate for describing the efficiency of SP polarimeters, especially when they are operated with time-structured excitation sources such as free-electron lasers. Numerical simulations have been performed and yield strong implications in the choice of the detecting instruments in spin-polarization experiments, that are constrained in a limited measurement time. Our results are therefore applied to the characteristics of a wide set of state-of-the-art spectroscopy facilities all over the world, and an efficiency diagram for SP experiments is derived. These results also define new mathematical instruments for handling the correct statistics of SP measurements in the presence of source intensity fluctuations.

Design and optimization of a modular setup for measurements of three-dimensional spin polarization with ultrafast pulsed sources.

ULTRASPIN is an apparatus devoted to the measurement of the spin polarization (SP) of electrons ejected from solid surfaces in a UHV environment. It is designed to exploit ultrafast light sources (free electron laser or laser high harmonic generation) and to perform (photo)electron spin analysis by an arrangement of Mott scattering polarimeters that measure the full SP vector. The system consists of two interconnected UHV vessels: one for surface science sample cleaning treatments, e-beam deposition of ultrathin films, and low energy electron diffraction/AES characterization. The sample environment in the polarimeter allows for cryogenic cooling and in-operando application of electric and magnetic fields. The photoelectrons are collected by an electrostatic accelerator and transport lens that form a periaxial beam that is subsequently directed by a Y-shaped electrostatic deflector to either one of the two orthogonal Mott polarimeters. The apparatus has been designed to operate in the extreme conditions of ultraintense single-X-ray pulses as originated by free electron lasers (up to 1 kHz), but it allows also for the single electron counting mode suitable when using statistical sources such as synchrotron radiation, cw-laser, or e-gun beams (up to 150 kcps).

Chronic headaches: a clinician's experience of ICHD-3 beta.

The International Classification of Headache Disorders, 3rd edition (beta version) has significantly improved the categorization of chronic headaches. From a clinical standpoint, however, it still has a few limitations, both general and specific. Among the former is the fact that international headache classifications are aimed less at defining the disease than at characterizing the features of attacks, meaning that their structure is ill suited to dealing with chronic headaches where the patient must be the focus of the discussion. Among the latter is the fact that the diagnostic criteria for chronic migraine do not distinguish between cases differing widely in severity and that the issue of whether medication overuse headache can be considered an autonomous entity is still unsolved. We propose that changes be made in the systematizations of chronic migraine and medication overuse headache to make them more consistent with clinical practice.

The PACE study: past-year prevalence of tension-type headache and its subtypes in Parma's adult general population.

The mean global prevalence of tension-type headache (TTH) in adult is 42 %. To date, there have been no Italian studies on TTH prevalence in the adult general population. Therefore, we conducted a cross-sectional study, called PACE, aimed at detecting the prevalence of primary headaches in the city of Parma's adult general population. 904 subjects representative of Parma's adult general population were interviewed face to face by a physician of our Headache Centre. Crude past-year prevalence for definite TTH was 19.4 % (95 % CI 16.8-21.9; 18.4 %, 95 % CI 14.6-22.3 in men, and 20.1 %, 95 % CI 16.6-23.6 in women), namely, 9.0 % (95 % CI 7.1-10.8) for infrequent TTH, 9.8 % (95 % CI 7.9-11.8) for frequent TTH, and 0.6 % (95 % CI 0.1-1) for chronic TTH. Crude prevalence for probable TTH was 2.3 % (95 % CI 1.3-3.3; 2 %, 95 % CI 0.6-3.4 in men, and 2.6 %, 95 % CI 1.2-3.9 in women). Our results indicate a TTH prevalence (19.4 %) at the lower limit of data ranges for Western countries, and prevalence rates for infrequent forms (9 %) do not appear different from those of frequent forms (9.8 %).

Symptomatic treatment of migraine: from scientific evidence to patient management.

All migraine patients need symptomatic treatment to stop individual attacks or, at least, significantly relieve pain. When attacks are very frequent (more than 3 days of headache per month on average), they will also need preventive treatment. The first physician the patient must address to for preventive treatment is the general practitioner (GP). If the medication prescribed by the GP is not effective or there is overuse of symptomatic drugs, the patient will have to be referred to a neurologist or a headache clinic. The drugs to be used as symptomatic treatment are triptans and non-steroidal anti-inflammatory drugs. Combination therapy with antiemetics is also important. While specialists will base their therapeutic decisions on guidelines in the literature and on their personal experience, GPs do not yet have any easy-to-use tools to support them. To fill this gap, an algorithm is proposed here that can be easily used by GPs to make decisions during their patients' migraine attacks.

Electric control of magnetism at the Fe/BaTiO3 interface.

Interfacial magnetoelectric coupling is a viable path to achieve electrical writing of magnetic information in spintronic devices. For the prototypical Fe/BaTiO3 system, only tiny changes of the interfacial Fe magnetic moment upon reversal of the BaTiO3 dielectric polarization have been predicted so far. Here, by using X-ray magnetic circular dichroism in combination with high-resolution electron microscopy and first principles calculations, we report on an undisclosed physical mechanism for interfacial magnetoelectric coupling in the Fe/BaTiO3 system. At this interface, an ultrathin oxidized iron layer exists, whose magnetization can be electrically and reversibly switched on and off at room temperature by reversing the BaTiO3 polarization. The suppression/recovery of interfacial ferromagnetism results from the asymmetric effect that ionic displacements in BaTiO3 produces on the exchange coupling constants in the interfacial-oxidized Fe layer. The observed giant magnetoelectric response holds potential for optimizing interfacial magnetoelectric coupling in view of efficient, low-power spintronic devices.

Reentrant surface anisotropy in the antiferromagnetic/ferromagnetic bilayer Mn/Co/Cu(001).

We investigated the magnetic anisotropy energy of monatomic surface-step atoms in antiferromagnetic/ferromagnetic (AF/FM) epitaxial Mn/Co bilayers grown on vicinal Cu(001) surfaces. The step-induced anisotropy of the Co/Cu(001) films was quenched upon submonolayer Mn deposition, but a reentrant uniaxial surface anisotropy was observed for Mn thickness (tMn) between 1 and 2 monolayers, which disappears for Mn thickness above 2 monolayers. In the Mn/Co/Cu(001) system, Mn films undergo a tMn-dependent transition from FM to AF in the 1-2 Mn monolayer thickness range, which entails the coexistence of FM and AF Mn phases in the film. The observation of a sizeable uniaxial anisotropy exclusively in the Mn-thickness range of coexistence of the FM and AF phases points out the crucial role of the boundaries between FM and AF regions within the Mn film. A symmetry-breaking mechanism of a magnetic type, rather than a purely geometric one, is therefore proposed as the origin of the reentrant anisotropy.

Parvovirus B19 associated acute cholestatic hepatitis.

There are few reports in the literature of hepatitis as a manifestation of Parvovirus B19 infection. We describe a case of Parvovirus B19 associated acute cholestatic hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in peripheral blood. Parvovirus B19 infection should be considered in the differential diagnosis of patient presenting with acute hepatitis of unknown etiology.

Identifying the electronic character and role of the Mn states in the valence band of (Ga,Mn)As.

We report high-resolution hard x-ray photoemission spectroscopy results on (Ga,Mn)As films as a function of Mn doping. Supported by theoretical calculations we identify, for both low (1%) and high (13%) Mn doping values, the electronic character of the states near the top of the valence band. Magnetization and temperature-dependent core-level photoemission spectra reveal how the delocalized character of the Mn states enables the bulk ferromagnetic properties of (Ga,Mn)As.

Chronification of migraine: what clinical strategies to combat it?

Once migraine becomes chronic and has transformed into a form of headache that occurs daily or almost, the treatment options available are few and complex. This makes it important to take action before this point is reached, using all the measures that can be obtained from our current knowledge of chronic migraine (or transformed migraine) on the one hand, and on the potential factors of chronification (or transformation) on the other. Therefore, in order to reduce the risk of migraine chronification, it would appear important to: (a) administer suitable preventive treatments for subjects who have been suffering from migraines ≥4 days a month for ≥3 months; (b) take special care not to overuse symptomatic medications, particularly when they contain substances with a sedative effect; and (c) investigate the concomitant presence of depression, hypertension and excess weight and administer appropriate treatment when present.

Prevalence of tension-type headache in adult general population: the PACE study and review of the literature.

The mean global prevalence of tension-type headache (TTH) in adult is 42 %. To date, there have been no Italian studies on TTH prevalence in the adult general population. Therefore, we conducted a cross-sectional study, called PACE (PArma CEfalea, or "Headache in Parma"), aimed at detecting the prevalence and clinical features of primary headaches in the city of Parma's adult general population. Crude past-year prevalence for definite TTH was 19.4 % (95 % CI 16.8-21.9), namely 9.0 % (95 % CI 7.1-10.8) for infrequent TTH, 9.8 % (95 % CI 7.9-11.8) for frequent TTH, and 0.6 % (95 % CI 0.1-1) for chronic TTH. Crude prevalence for probable TTH was 2.3 % (95 % CI 1.3-3.3). Our study results indicate a TTH prevalence rate (19.4 %) at the lower limit of data ranges currently available for Western countries, and prevalence rates for infrequent forms (9 %) do not appear much different from those of frequent forms (9.8 %).

Proximity effects and exchange bias in Co/MnF2(111) heterostructures studied by x-ray magnetic circular dichroism.

Cobalt nano-structured ultrathin films were grown on orthorhombic MnF(2) by molecular beam epitaxy on CaF(2) epitaxial layers deposited on Si(111) substrates. The Co film was grown at room temperature. It was found to be polycrystalline, forming nano-islands with height≈diameter≤10 nm. X-ray absorption evidences the chemical stability of the Co/MnF(2) interface. Remarkably, x-ray magnetic circular dichroism (XMCD) demonstrates that the Co induces a net magnetization on the Mn ions close to the interface. The magnetic moments of these Mn ions couple antiparallel to the Co and rotate upon field reversal following the magnetization of the Co both below and high above the Néel temperature of MnF(2) (T(N) = 67 K). The density of coupled Mn moments is found to be temperature dependent, with an equivalent thickness of ~1.5 MnF(2) monolayers at 20 K, decreasing to about ~0.5 ML as the temperature is raised to 300 K. Interestingly, the intensity of the Mn XMCD signal appears to be related to the coercivity of the Co layer. This behavior is interpreted in terms of the competition between thermal fluctuations, exchange coupling between Co and Mn at the interface and, at low temperature, the antiferromagnetic order in MnF(2).

Growth of ultrathin epitaxial Fe/MgO spin injector on (0, 0, 1) (Ga, Mn)As.

We have grown an ultrathin epitaxial Fe/MgO bilayer on (Ga, Mn)As by e-beam evaporation in UHV. The system structure has been investigated by high resolution transmission electron microscopy (TEM) experiments which show that the Fe and MgO films, covering completely the (Ga, Mn)As, grow with the epitaxial relationship Fe[100](001) [parallel] MgO[110](001) [parallel] (Ga,Mn)As[110](001). The magnetic reversal process, studied by the magneto-optical Kerr effect (MOKE) at room temperature, demonstrates that the iron is ferromagnetic and possesses a cubic anisotropy, confirming the epitaxy relationship found with TEM. Resistivity measurements across the barrier display a non-Ohmic behavior characterized by cubic conductance as a function of the applied voltage suggesting tunneling-dominated transport across the barrier.

New prospects in the taxonomic classification of primary headaches.

In the field of primary headaches, we have a very useful classification tool for the clinical characterization of individual attacks, but we lack a classification tool for the characterization of primary headache patients. Just because the reasons for this lack have been partially overcome by the knowledge that has been gained in the meantime and because clinicians and researchers are increasingly pressed to find new and reliable ways to manage certain primary headache forms, including so-called chronic migraine, we now have an imperative commitment to provide a syndrome classification.

A redefinition of primary headache: chronic migraine.

In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. A proposal is advanced to differentiate between a form of high-frequency migraine without aura (10-20 days of headache per month for at least 3 months), to be considered as a migraine without aura subtype, and a form of transformed migraine (TM), to be considered as a complication of migraine. TM--a name that should be preferred to chronic migraine (CM)--would then replace the latter, from which it would distinguish itself by the more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days).