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The ability to produce atomically precise, artificial oxide heterostructures allows for the possibility of producing exotic phases and enhanced susceptibilities not found in parent materials. Typical ferroelectric materials either exhibit large saturation polarization away from a phase boundary or large dielectric susceptibility near a phase boundary. Both large ferroelectric polarization and dielectric permittivity are attained wherein fully epitaxial (PbZr0.8Ti0.2O3)n/(PbZr0.4Ti0.6O3)2n (n = 2, 4, 6, 8, 16 unit cells) superlattices are produced such that the overall film chemistry is at the morphotropic phase boundary, but constitutive layers are not. Long- (n ≥ 6) and short-period (n = 2) superlattices reveal large ferroelectric saturation polarization (Ps = 64 µC cm−2) and small dielectric permittivity (εr ≈ 400 at 10 kHz). Intermediate-period (n = 4) superlattices, however, exhibit both large ferroelectric saturation polarization (Ps = 64 µC cm−2) and dielectric permittivity (εr = 776 at 10 kHz). First-order reversal curve analysis reveals the presence of switching distributions for each parent layer and a third, interfacial layer wherein superlattice periodicity modulates the volume fraction of each switching distribution and thus the overall material response. This reveals that deterministic creation of artificial superlattices is an effective pathway for designing materials with enhanced responses to applied bias.

The ability to tailor a new crystalline structure and associated functionalities with a variety of stimuli is one of the key issues in material design. Developing synthetic routes to functional materials with partially absorbed nonmetallic elements (i.e., hydrogen and nitrogen) can open up more possibilities for preparing novel families of electronically active oxide compounds. Fast and reversible uptake and release of hydrogen in epitaxial ABO3 manganite films through an adapted low-frequency inductively coupled plasma technology is introduced. Compared with traditional dopants of metallic cations, the plasma-assisted hydrogen implantations not only produce reversibly structural transformations from pristine perovskite (PV) phase to a newly found protonation-driven brownmillerite one but also regulate remarkably different electronic properties driving the material from a ferromagnetic metal to a weakly ferromagnetic insulator for a range of manganite (La1−xSrxMnO3) thin films. Moreover, a reversible perovskite-brownmillerite-perovskite transition is achieved at a relatively low temperature (T ≤ 350 °C), enabling multifunctional modulations for integrated electronic systems. The fast, low-temperature control of structural and electronic properties by the facile hydrogenation/dehydrogenation treatment substantially widens the space for exploring new possibilities of novel properties in proton-based multifunctional materials.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12 +/- 3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.

The aim of this paper is to analyse the use of anti-TNF drugs in current Italian practice, evaluate clinical responses to treatment, and identify possible predictors of negative response in patients with rheumatoid arthritis (RA).DOSE is a non-interventional, prospective study of patients with active RA treated for the first time with anti-TNF agents in 21 Italian hospitals. Demographic and clinical characteristics of patients, treatments and outcome measures were assessed. Outcome measures used were EULAR response, DAS28 remission and HAQ remission at 12 months. A stepwise logistic regression model was used to study the predictors of non-response.Of 299 RA patients (mean 53.8 ± 12.8 years, 76.1% female), DAS28 was5.1 in 60.5% of patients and HAQ was1 in 65.9%. Etanercept was the most prescribed anti-TNF. DMARDs were used in 77.6% of patients (methotrexate in 59.2%). Significant improvements in clinical and laboratory parameters were observed at 12 months. The proportion of patients classed as non-responders remained high, and varied according to assessment criteria. The main predictors independently and significantly associated with a high risk of non-response were: age and female gender for all outcome criteria; high DAS28 value for disease remission; and HAQ1 for disability remission.In Italian anti-TNF treatment for RA, age, gender, and high values of both disease activity and disability were predictors of non-response to first-line therapy with anti-TNF drugs. Future studies should consider optimal second-line therapies for RA patients who do not achieve remission to their first anti-TNF treatment.

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The hemodynamic and gas exchange effects of 20 mg of nifedipine (NFD), at rest and exercise were evaluated in seven patients with unstable COPD and pulmonary hypertension. The cause of instability was pulmonary infection (n = 6) and pulmonary emboli (n = 1). At rest, pulmonary hypertension (Pp = 40 +/- 3 mmHg), severe hypoxemia (PaO2 +/- 2 mmHg) and elevated pulmonary vascular resistance (Rp) = 9 +/- .6 u.sq.m, were found. At exercise, Pp raised to 52 +/- 5 mmHg with no change in cardiac index (CI), Rp or gas exchange. After NFD at rest, significant (p less than 0.05) increases in CI, oxygen transport and venous admixture occurred. Also, Rp and systemic arterial pressure and resistance decreased significantly. Pp and blood gas exchange did not vary. Rp and systemic resistance were lower at exercise after NFD than without the drug with no change in blood gas exchange. The pulmonary flow pressure relationship showed a right shift after NFD in both, rest and exercise conditions. We conclude that NFD can be of value for the management of pulmonary hypertension that aggravates COPD.

To determine whether hydralazine (H) a systemic vasodilator, inhibits hypoxic pulmonary vasoconstriction (HPV) we studied in a canine model of lobar atelectasis (LA) the circulatory changes during the following interventions: a) control 1 (LA = HPV), b) during the acute effect produced by opening bilateral arteriovenous fistulas (OF), c) after the closure of the fistulas (CF) (control 2), d) after infusing H (0.33 mg/kg) and e) bleeding the animal at the end of the experiment (control 3). Once HPV was stabilized (control 1), both opening the fistulas and infusing H produced a similar and significant increase in cardiac output and a decrease in resistance (p less than 0.05). Mixed venous oxygen tension (PvO2) closely followed the changes in cardiac output (Qt). Intrapulmonary shunt (Qs/Qt) significantly increased (p less than 0.05) with the fistulas open and with H infusion. CF and bleeding the animal at the end of the experiment reversed the changes in Qt and Qs/Qt. The similar increases in Qt and Qs/Qt by OF or infusing H seems to be related to the levels of pVO2. Our data suggest that hydralazine inhibits pulmonary vasoconstriction probably by raising the level of pVO2 although a direct pulmonary vasodilatory effect of the drug could not be ruled out.

The role of active and passive factors involved in the genesis of Pulmonary Arterial Hypertension (PAH) is analyzed in a group of eighty patients with several cardiopathies and pneumopathies. The group include: 20 patients with Chronic Obstructive Lung Disease (NODC), 20 with Diffuse intersticial pneumopathy (NI), 12 with Cardiorespiratory Syndrome of the grossly obese (OB), 6 with Pulmonary Embolism (TEP), 6 with Mitral Stenosis (CRI), 5 with Hypertensive Ventricular Septal Defect (CIV + HAP) and 11 patients with Pulmonary Arterial Hypertension of Unknown etiology (HAP-ED). For the analysis, the Harvey and Enson's formulas were used. The conclusions of the study are: 1) The compliance of the elastic arteries of the lung in the groups of NOC, NI and OB is normal but in the other groups seems to be modified. 2) In the groups of NI and OB the interrelationship of factors such as alveolar hypoxia and pulmonary wedge pressure (PWP) play the major role in the genesis of PAH, although the role of the PaCO2 in the OB group remains to be established. 3) In the groups of NOC, CRI and TEP the PWP is not determinant. The absence of a significant correlation between arterial oxygen unsaturation and pulmonary diastolic pressure in the NOC group suggests other factors. 4) The vascular structural damage seems to be the most important factor in the genesis of PAH in the HAP-ED and CIV + HAP groups.

Salivary glands tumors constitute a highly heterogeneous group in human oncological pathology. They show different clinical, epidemiological, histopathological and evolutionary characteristics.In this paper we have analysed their epidemiological aspects in 454 patients with salivary glands tumors surgically treated at the Maxillofacial Surgical Unit of the Azienda Ospedaliero-Universitaria ''Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi'', Ancona, Italy, from 1990 to 2002, to evaluate the incidence of the different types of neoplasia and their age and sex distribution.Our results show that 63.22% of salivary glands tumors occur in the parotid gland, with a predominance of benign tumours, pleomorphic adenoma being the most prevalent histological type. A higher prevalence was observed in the female sex.Malignant tumors were more common in the elderly than in young patients and the most common histological types were mucoepidermoid carcinoma and adenoid cystic carcinoma.

The study aims to provide novel findings on geographic variation in the management of primary Sjögren's syndrome (pSS) in Europe, an underdiagnosed, long-term autoimmune disease.Starting from the lack of comparable information on patients' experience, quality and efficiency of care delivered to pSS patients in Europe, the approach is to collect and analyse patients reported data from an international survey. To assess and compare access and quality of care to pSS along their care-path we developed and validated a questionnaire administered to a large cohort of pSS patients in selected European countries. Regression models have been applied to survey data to compare quality and volumes of care across Europe.Both follow-up and number of visits with a specialist of the patient are influenced by the severity of the disease with differences among countries. The results show some extent of variations in access and treatments delivered to pSS patients and also their perceived quality of life and satisfaction for SS care in Europe.Findings contribute to support healthcare professionals' decision making and the organisation of care delivery by taking into consideration the patients' point of view and preferences.

Acetyl-salicylic acid inhibits thromboxane A2 production and reduces the risk of vascular occlusive events by 20 to 25%. Ticlopidine inhibits ADP-dependent platelet aggregation and reduces the same risk by 30 to 35%, but produces some adverse effects. Clopidogrel is a ticlopidin-derived antiplatelet-drug, with the same mechanism of action; reduces the expression of the glycoprotein IIb/IIIa, the fibrinogen receptor on the platelet surface. Clopidogrel has the same clinical efficacy of ticlopidin and lowers the incidence of adverse effects. In this study, we evaluated the effects of one daily dosis of 75 mg of clopidogrel on platelet function in 33 subjects with coronary artery disease. Before treatment and after the 6th and 12th week, the following parameters were evaluated: 5 microM-ADP and 20 micrograms/mL collagen-induced platelet aggregation, bleeding time and fibrinogen concentration. In basal and in the 6th and 12th week samples, ADP-induced platelet aggregation was 90.7% +/- 13.2, 54.6% +/- 23.2 and 49.2% +/- 23.7 respectively, that represents a significant reduction of 38.6% and 44.4%. Reduction of collagen-induced platelet aggregation was not significative. Plasmatic fibrinogen did not suffer variation during treatment. Bleeding time was significant prolonged from 4.1 minutes to 15.4 and 14.6 minutes (3.7-3.5 times compared with the test before treatment). There were no haemorrhagic complications, only digestive discomfort in fewer than 3% of patients. We concluded that clopidogrel is a safe and efficacious drug for patients, it efficiently reduces ADP-induced platelet aggregation and prolongs bleeding time.