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Geological survey and geochronological analyses were conducted in the Campo Imperatore plain to understand its Quaternary morpho-sedimentary and tectonic evolution. In the Late Pliocene-Early Pleistocene, low relief energy and steady and warm climatic conditions promoted a long phase of areal peneplanation, resulting in the formation of gently sloping landscape. With further regional uplift and changes in frequency/amplitude of the glacial-interglacial cycles (Early-Middle Pleistocene transition) and after establishment of the expansion-contraction cycles of the Apennine glaciers (Middle Pleistocene), the morpho-sedimentary processes become highly dynamic. In Middle Pleistocene, more than 100 meters of breccias deposited all along the slopes of the Gran Sasso range, followed by higher frequency processes of sedimentation, erosion and pedogenesis of Middle-Late Pleistocene to Holocene fluvio-glacial deposits. These have been progressively offset by synthetic and antithetic normal faults belonging to the Gran Sasso fault system, a 40-km-long seismogenic structure which released in the past earthquakes of Mw~7. [ABSTRACT FROM AUTHOR]

The measurement of spin noise in nuclei was demonstrated on bulk samples more than two decades ago. An ensemble of spins can produce a coherent signal at the Larmor frequency of a static magnetic field, known as spin noise, an effect due to the statistical polarization of small ensembles. The difficulty of these measurements is that the signal is extremely small—even if electron spins are detected. Although the statistical polarization of N spins dominates the Boltzmann statistics if N approaches unity, a more sensitive tool is requested to measure the polarization of the magnetic moment of a single spin. In this paper we report on the verification of recent results on the detection of spin noise from paramagnetic molecules of α,γ-bisdiphenylene-β-phenylallyl (BDPA) by Durkan and Welland [Appl. Phys. Lett. 80, 458 (2002)]. We also present results on a second paramagnetic specie 1,1-diphenyl-2-picrylhydrazyl (DPPH), deposited on Au(111) surfaces. Electron spin resonance spectra from ultrathin films of DPPH and BDPA grown on Au(111) are reported. We prove that the paramagnetic molecules preserve their magnetism on the surface. These data and a thorough analysis of the signal recovery apparatus help us to understand the low statistical recurrence of the spin noise in the data set. A detailed description of the experimental apparatus together with an analysis of the parameters that determine the sensitivity are also presented. [ABSTRACT FROM AUTHOR]

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of “don't know” answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors. [ABSTRACT FROM AUTHOR]

The aim of this study was to verify whether abnormalities in plasma amino acid (AA) levels could be biological correlates of the age of onset in amyotrophic lateral sclerosis (ALS). We undertook plasma AA profiling in a large population comprising 117 newly diagnosed ALS patients and 117 matched controls. ALS patients were stratified in early (58 patients aged < 55 years) versus late onset (59 patients aged > 74 years). We applied a rapid and reproducible method for the analysis of AA using amine reactive isotope coded tags in conjunction with liquid chromatography coupled to Multiple Reaction Monitoring-Mass Spectrometry. Results showed that values of only three AA were significantly different in ALS patients and controls. We found lower levels of leucine and higher levels of glutamate and leucine in early-onset ALS compared to their matched controls. In conclusion, different AA patterns related to the ALS age of onset were found, providing insight into possibly aberrant biochemical pathways that might unlock key pathological pathways. [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy, safety and tolerability of sodium valproate (800 mg/die) compared with placebo in medication-overuse headache patients with a history of migraine without aura. Methods This is a multicenter, randomized, double-blind, placebo-controlled study enrolled medication-overuse headache patients for a 3-month treatment period with sodium valproate (800 mg/day) or placebo after a 6 day outpatient detoxification regimen, followed by a 3-month follow-up. Primary outcome was defined by the proportion of patients achieving ≥50% reduction in the number of days with headache per month (responders) from the baseline to the last 4 weeks of the 3-month treatment. Multivariate logistic regression models were used on the primary endpoint, adjusting for age, sex, disease duration, comorbidity and surgery. The last-observation-carried-forward method was used to adjust for missing values. Results Nine sites enrolled 130 patients and, after a 6-day detoxification phase, randomized 88 eligible patients. The 3-month responder rate was higher in the sodium valproate (45.0%) than in the placebo arm (23.8%) with an absolute difference of about 20% ( p =0.0431). Sodium valproate had safety and tolerability profiles comparable to placebo. Conclusions The present study supports the efficacy and safety of sodium valproate in the treatment of medication overuse headache with history of migraine after detoxification. [ABSTRACT FROM AUTHOR]

Objective To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). Methods From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1,166 population controls (matched for age, sex, and residency) were assessed. Upon direct interview, data were collected on occupation and history of sport and leisure activities, physical activity, and accidental injuries. Physical exercise was defined as having spent time doing activities that caused an individual to breath hard at least once per month and was coded as none, job-related, and/or sport-related. Sport-related and work-related physical exercise were quantified using metabolic equivalents (METs). Risks were calculated using conditional logistic regression models (adjusting for age, country, trauma, and job-related physical activity) and expressed as odds ratios (ORs) and adjusted ORs (Adj ORs) with 95% confidence intervals (CIs). Results Overall physical activity was associated with reduced odds of having ALS (Adj OR = 0.65, 95% CI = 0.48-0.89) as were work-related physical activity (Adj OR = 0.56, 95% CI = 0.36-0.87) and organized sports (Adj OR = 0.49, 95% CI = 0.32-0.75). An inverse correlation was observed between ALS, the duration of physical activity ( p = 0.0041), and the cumulative MET scores, which became significant for the highest exposure (Adj OR = 0.34, 95% CI = 0.21-0.54). An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events. Interpretation Physical activity is not a risk factor for ALS and may eventually be protective against the disease. ANN NEUROL 2014;75:708-716 [ABSTRACT FROM AUTHOR]

Abstract: A questionnaire survey was undertaken to assess the impact of a nationwide educational campaign about epilepsy on the knowledge and attitudes toward the disease among Italian primary school teachers. Five hundred and eighty-two teachers participated. All interviewees were aware of the existence of epilepsy, and most of them had direct experience with the disease. Answers about frequency, causes, outcome, and response to treatments were variable and not correlated with age, residency, and years of experience. Teachers had positive attitudes toward epilepsy, except for the idea that driving and sports can be safe for people with epilepsy. Epilepsy and its treatment were considered a source of learning disability and social disadvantages. Several teachers declared themselves being unable to help a child having seizures. Calling an ambulance was a frequent action. Knowledge and attitudes toward epilepsy are improved compared with those reported in our previous studies. Although this may be a positive reflection of the increasing knowledge and the greater availability of information on epilepsy, there are still areas of uncertainty and incorrect behaviors. [Copyright &y& Elsevier]

ALS is a heterogeneous disease that is not well understood. Epigenetic rearrangements are important in complex disorders including motor neuron diseases. The aim of this study was to determine whether whole-blood DNA methylation (DNA MET %) is a potential modifier of age at onset in ALS. DNA MET % was measured as incorporation of [3H]dCTP following HpaII cut in 96 ALS patients and 87 controls, comprising: early-onset (< 55 years of age) and late-onset (> 74 years of age). Methionine (Met) and homocysteine (Hcy) plasma levels were assessed by liquid chromatography selected reaction monitoring coupled with isotope-dilution mass spectrometry. Results showed that DNA MET % was increased in ALS patients independently of age of onset. Compared to the other three groups, Hcy plasma levels were reduced in early-onset ALS patients but Met levels were similar. ROC analysis reported Met levels and DNA MET %, respectively, with a slight and moderate discriminative power. In conclusion, increased DNA MET % is a possible marker of epigenetic dysfunction in ALS independently of age of onset. Further studies dissecting biological determinants of phenotypic complexity in ALS may help in developing successful therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective To determine the long-term survival in amyotrophic lateral sclerosis (ALS) and identify predictors of prolonged survival in a population-based cohort of newly diagnosed patients. Methods An incident cohort from a population-based registry during the years 1998 through 2002 in Lombardy, Italy was followed until death or to February 28, 2013. Age, sex, date of onset of symptoms, site of onset, date of diagnosis, and El Escorial diagnostic category were collected. Survival was assessed using Kaplan-Meier curves. Cox proportional hazards function was used to identify independent prognostic predictors. Standardized mortality ratios (SMRs) were used to assess the 5-year and 10-year excess mortality of ALS patients. Results Included were 280 men and 203 women aged 18 to 93 years. Spinal onset ALS was present in 312 cases (64.6%). Definite ALS was diagnosed in 213 cases (44.1%), probable ALS in 130 (26.9%), possible ALS in 93 (19.3%), and suspected ALS in 47 (9.7%). The cumulative time-dependent survival at 1, 5, and 10 years from diagnosis was 76.2%, 23.4%, and 11.8%, respectively. Independent predictors included younger age, the diagnosis of possible/suspected ALS, spinal onset, and symptoms having started >12 months previously at diagnosis. SMR was 9.4 at 5 years and 5.4 at 10 years. SMR at 10 years was higher until age 75 year, predominating in women, and became nonsignificant for males thereafter. Interpretation The outcome in ALS varies with phenotype. Longer survival is predicted by younger age, spinal onset, male gender, and suspected ALS. After age 75 years, 10-year survival in men with ALS is similar to the general population. Ann Neurol 2014;75:287-297 [ABSTRACT FROM AUTHOR]

Abstract: Epilepsy surgery (ES) in pediatrics is safe and effective but can be underutilized. Possible barriers could be parental resistance and doctor inertia. We surveyed 138 parents of pediatric patients with epilepsy and found that 25.2% were opposed to this treatment. However, upon completing the questionnaire that contained factual information about ES, 50.4% of the responders stated that they had become more favorable vs. 3.3% more contrary and 46.3% unchanged. Parents of prepubescent patients were most receptive (p=0.0343) and more likely to shift to a more favorable attitude. Thus, pediatric neurologists should not hesitate to discuss ES as soon as indicated, providing all necessary information to increase acceptance. However, among 60 child neurologists surveyed, 60% did not fully comply with guidelines or follow accepted standards of practice, indicating that they may not be apt to provide proper parental guidance. We conclude that education of both practicing neurologists and parents is needed to facilitate the process. [Copyright &y& Elsevier]

Abstract: Physician inertia is usually blamed for the underutilization of epilepsy surgery (ES) at the cost of increased patient disability and risk of mortality. Investigations on selected groups of patients with intractable TLE and minorities suggested that patient beliefs may also limit access to ES. To assess acceptance of ES among “mainstream” patients, we distributed an ad hoc questionnaire to 228 adults attending epilepsy clinics and found widespread fears and misconceptions leading to unfavorable perception of ES, irrespective of diagnosis, seizure type, and degree of intractability. Moreover, while a group firmly rejected ES, the majority became more favorable when given further information about modality, rationale, and expected outcome of ES. Attitude changes correlated with patient''s social profile. Neurologists are responsible for providing all pertinent information to potential surgical candidates as soon as indicated. Therefore, an untimely or inadequate intervention of the treating physician constitutes an additional barrier to optimal utilization of ES. [Copyright &y& Elsevier]

Summary: Purpose: To assess incidence, indicators and outcome of satisfaction with antiepileptic drugs in children. Methods: Multicenter, observational, open, prospective survey of children and adolescents with epilepsy with three-month follow-up. Included were patients aged 3–17 years with newly diagnosed (“new diagnosis”) or chronic epilepsy (“old diagnosis”) requiring treatment start or change. Satisfaction was assessed with the Hedonic Visual Scale or direct questions, depending on patient''s age. Quality of life of adolescents (QOLIE-48) and of caregivers (SF-36) and predictors of (dis)satisfaction were also assessed. Results: 293 patients completed the study. Most had generalized idiopathic epilepsy, and a disease lasting <12 months. Newly diagnosed patients were 60.8%. Patients declaring satisfaction were 70.6% at one month and 75.8% at three months. Compared to old diagnosis, new diagnosis carried a higher satisfaction rate and improved satisfaction at end of follow-up. Independent predictors of dissatisfaction were an old diagnosis, adverse events and SF-36 score. The latter remained the only independent predictor of persisting dissatisfaction when adjusting for the presence of and the interaction with adverse events. Conclusions: About one-fourth of children and adolescents with epilepsy are dissatisfied with treatment. Chronic epilepsy, adverse events, and parents/caregivers with poor quality of life predict dissatisfaction. [Copyright &y& Elsevier]

Abstract: Amyotrophic lateral sclerosis (ALS) clinical trials suffer a large proportion of drop-outs. Ignoring missing data can lead not only to underpowered tests, but also to selection bias. Current strategies for handling not at random missing data have several limitations. To determine the most effective approach, we compared the standard procedures with the pattern mixture model, using the data from a randomized dose-finding trial on lithium for the treatment of ALS, which reported a high rate of drop-outs (68.4%). We evaluated the ALS Functional Rating Scale-Revised (ALSFRS-R) profile using mixed effect models on different reference populations (1. Intention-to-treat, 2. “Completers”, 3. Last observation carried forward, 4. “0-imputation”). All four strategies have limitations on account of: 1. Violation of the “missing completely at random” assumption of the mixed model; 2. Underpowered results on selected patients; 3. Underestimation of the time effect on ALSFRS-R decline and misuse of the assumption that those who discontinued could not get worse; 4. Overestimation of the time effect on ALSFRS-R decline and misuse of the assumption that those who discontinued could not have scores different from zero. The pattern mixture models fitted better than models that did not consider the missing data pattern effect (p=0.006 and p=0.0002). Pattern mixture model thus seem superior and we recommend its use to obtain more accurate estimates even when the information is missing. [Copyright &y& Elsevier]

The evolution of the Apennine arc is related to the flexural retreat of the Adriatic lithosphere plate, the NE migration of the compressive front and the contemporaneous rifting of the Tyrrhenian basin. Evidence of the NE migration of the orogen can also be inferred from the analysis of the intra-Apennine Quaternary extensional tectonics. Stratigraphic and structural data collected along NE–SW transects in the Abruzzi Apennines (central Italy), indeed, indicate that the westernmost normal faults (activated during the Pliocene) have to be considered inactive since the Early Pleistocene (Turano valley fault) or the beginning of the Middle Pleistocene (Salto valley and Liri valley faults). In contrast, the easternmost faults (Campo Imperatore and Mt. Morrone faults) were activated during the Early Pleistocene and are still active, as demonstrated by the displacement of Late Pleistocene–Holocene deposits and landforms. Within the innermost portion of the extensional domain, the Fucino and upper Aterno valley fault systems show persistent activity since the Pliocene. Besides the evidence of a progressively NE-shifted intra-Apennine extension, available data suggest that a period of co-existing activity of the presently inactive and newly activated faults (e.g. Liri valley and Mt. Morrone faults, respectively) occurred during the Early Pleistocene. This indicates that for a few hundred thousand years active faults in the central Apennines were more numerous than in the period of the present tectonic regime. This may have resulted in a reduced activity per fault (lower slip rates) or an increased intra-Apennine extension rate. Quaternary faults in the Abruzzi Apennines generally coincide with pre-existing discontinuities such as old thrust ramps or syn-orogenic normal faults. Based on a simple geometric criteria, i.e. direction, dip, length of the pre-existing discontinuities located east of the investigated area, and assuming a still active NE-migration of the extensional domain, it is possible to hypothesize that the old and presently inactive normal faults of the Maiella and Montagna dei Fiori anticlines may accomodate active extension of the future. The NE-ward shifting of the extensional domain would be, instead, locked if the process of lithospheric flexural retreat which drove the Neogene-Quaternary p.p. structural evolution of the Apennine chain has ended during the Early Pleistocene. [Copyright &y& Elsevier]

Remants of a flat paleolandscape of erosional origin (top paleolandscape, TPL) have been detected in the Abruzzi Apennines (central Italy) at high elevations (1350–1500 m a.s.l.). According to current views, the TPL formation occurred at an elevation close to sea level, and probably marks the first significant geomorphic event in the investigated sector. Since this erosional paleolandscape affects an already deformed pre-Pliocene marine substratum and different structural units, its formation occurred after the thrust-faulting phase, which affected the investigated area. The present elevation of the TPL remnants indicates a significant uplift following the formation of this geomorphic feature. This uplift began during the Pliocene (age of the first post-thrusting continental deposits, subsequent or sub-contemporaneous to the TPL and related to the formation of intermontane basins). Pliocene deposits have been found in the Turano, Salto, and Fucino basins. The origin of these basins was conditioned by the activity of normal faults, which affected and displaced the TPL during the Pliocene. Considering (1) that the TPL experienced uplift since the Pliocene and (2) that after the beginning of the uplift phase it was displaced during the Pliocene by the faults responsible for the evolution of the mentioned basins, uplift of the Apennine chain and normal faulting are closely related. The analysis of the mentioned basins permitted to hypothesise a succession of Pliocene–early Pleistocene geomorphic and tectonic events: (1) Pliocene formation of the TPL at low elevation a.s.l.; (2) beginning of the uplift and displacement of the TPL due to the activity of normal faults; (3) formation of the Turano, Salto, and Fucino Pliocene basins; (4) fault activity responsible for the displacement of the Pliocene deposits; (5) erosional phase affecting all the investigated basins; (6) deposition of the Early Pleistocene units. [Copyright &y& Elsevier]

Terra Nova, 23, 280-282, 2011 Abstract We question the approach followed by the Authors in identifying a presumed 'new' fault, and particularly the uncritical use made of topographic profiles, in which morphological features of different ages and origins are crudely correlated, creating the fake image of fault-tilting. We also point out the incorrect age attribution of faulted deposits - assumed without any analytical determination and/or stratigraphical framework - which has yielded serious errors as far as the timing of fault activity is concerned. These mistakes have led to incorrect conclusions and unavoidable repercussions for seismic hazard assessment of a region which has been just tragically struck by a disruptive earthquake. [ABSTRACT FROM AUTHOR]

Discusses single-molecule level scanning tunneling microscopy observations of chiral complexes generated by the assembly of achiral components and metal centers at a metal surface. Co-deposition of iron atoms and trimesic acid on a Cu(100) surface under ultrahigh vacuum conditions; Factors that account for the compact arrangement of molecules in the complexes.

An integrated investigation including geological, geomorphological, geophysical and structural survey, tephra analyses, 14 C and 40 Ar/ 39 Ar dating, as well as paleoseismic trenching along the N-Matese fault system is presented. The study allowed the characterization of the tectonic mobility of this structure as well as the associated Bojano basin sedimentary-tectonic evolution since the early Middle Pleistocene, providing also new clues concerning the fault historical activity and the associated Mw > 6.5 earthquakes. We have found lines of evidence for > 1 mm/yr slip rate along the presently buried Bojano fault during the mid Middle Pleistocene, and similar rates for the main fault segments paralleling the Matese flanks. The buried Bojano fault significantly slowed down during the last 300 kyr, ceasing its activity before the Holocene. In turn, the segments outcropping along the Matese flanks reactivated at the onset of Late Pleistocene, after a long period of quiescence (480–110 ka), with robust slip rates that would seem even accelerating in post LGM times. Paleoseismic data suggest the occurrence of four Mw > 6.6 earthquakes in the past 3 ka, three of which match the little known 280 BC event, and the devastating 1456 and 1805 earthquakes. [ABSTRACT FROM AUTHOR]

New palaeoseismic trenching across the main splay of the Fucino fault system provides evidence for a High Middle Age surface-faulting episode conceivably associated with a disruptive earthquake, similar to the one that occurred in 1915 (Mw 7.0). The existence of this event, which has already been suggested by some previous studies, implies a shortening of the recurrence interval for Mw 7.0 earthquakes with respect to current knowledge. If we assume that the palaeoseismic Holocene record is complete, this shortening is focused in the historical period, when the Fucino structure sourced three strong earthquakes in only 1.4 ka. A similar clustering of energy release in the recent past is consistent with both palaeoseismological studies on other faults affecting the Apennine divide, and the high GPS strain rates observed in the same chain sectors. [ABSTRACT FROM AUTHOR]

Our objective was to assess the association between amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia (FTD) and Parkinson's disease (PD). From May 2007 through August 2012 we investigated 146 patients with newly diagnosed ALS and 146 age- and gender-matched controls. Each individual was screened for cardinal extrapyramidal signs (neurological examination) and cognitive dysfunction (Mini Mental State Examination, MMSE and Frontal Assessment Battery, FAB). Results demonstrated that rigidity was present in 8.2% of cases and 2.1% of controls (adjusted odds ratio, adjOR 5.7; 95% CI 1.5–22.0). The corresponding percentages for bradykinesia and postural instability were, respectively, 8.2 vs. 2.7% (adjOR 4.8; 95% CI 1.4–16.5) and 2.7 vs. 9.6% (adjOR 0.3; 95% CI 0.1–0.9). FAB ≤ 13.4 was recorded in 24.8 vs. 9.6%; adjOR 2.9; 95% CI 1.5–5.7). Tremor and abnormal FAB score were predicted by an older age at onset while an abnormal FAB score was associated with cramps and family history of neurodegenerative diseases. In conclusion, our data support the notion that newly diagnosed ALS carries a higher than expected risk of extrapyramidal signs and FTD. [ABSTRACT FROM PUBLISHER]

Introduction Ureteropelvic junction obstruction (UPJO) is the most common pediatric obstructive uropathy. We report our 8-year experience with the use of a retroperitoneal laparoscopic-assisted pyeloplasty (one-trocar-assisted pyeloplasty [OTAP]). Materials and Methods This is a retrospective analysis of 88 patients treated in 8 years. Surgery was performed on the basis of standard indications and it consisted of 88 OTAP (the ureteropelvic junction is identified through a retroperitoneoscopic inspection and it is exteriorized to perform a traditional dismembered pyeloplasty). Operative time, hospital stay, complication, success of the technique, and aesthetical results are analyzed. Results In the 8-year period we performed 88 OTAP. Mean age was 19 months. Prenatal diagnosis was the most common presentation (n = 73), followed by occasional identification (n = 8), and symptomatic (n = 7). Mean operating time was 139 minutes (range 60-225 minutes). Conversion was required in seven cases. The success rate was 87.5% (reduction of the severity of hydronephrosis on ultrasound) and 100% among symptomatic patients (symptoms resolution). Aesthetical results were excellent. Discussion and Conclusions OTAP is safe, feasible, and efficacious. Operative times are similar or even shorter than those of other minimally invasive techniques and complication rate agrees with the findings of literature. OTAP can be considered a reasonable alternative. [ABSTRACT FROM AUTHOR]

Objective To calculate prevalence and incidence of epilepsy using administrative records. Methods Claim records from the administrative district of Lecco, Northern Italy (population 311,637; 2001 census), collected during the years 2000-2008, were the data source. Patients of all ages were included. Based on previous findings from our group, the most accurate algorithm to detect epilepsy was the combination of electroencephalography ( EEG) (ad hoc code) (at least one during the study period) and antiepileptic drugs ( AEDs) ( ATC code) (taken in 2008). Using this algorithm, the prevalence of epilepsy for the year 2008 was calculated. The reference population for prevalence was the population residing in the study area during the year 2008. Incident epilepsy cases were a subset of prevalent cases among patients not traced in the years 2000 through 2003. Average annual incidence rates were calculated for 2004 through 2008, taking for reference the person-years of exposure in the resident population. We calculated crude, adjusted (using positive and negative predictive values), and standardized (to the Italian and World population) prevalence and incidence. Results In 2008, 1,504 patients met the inclusion criteria, giving a prevalence of 4.57 per 1,000 (women 4.26; men 4.89). Prevalence tended to rise slightly with age. There were 864 incident cases, giving an average annual incidence of 53.41 per 100,000 (women 50.98; men 55.95). Incidence rates peaked in the elderly. The adjusted prevalence was 4.42 and the adjusted incidence 47.05. Standardized prevalence and incidence were, respectively, 4.30 per 1,000 and 48.35 per 100,000 (Italian population) and 3.79 per 1,000 and 44.74 per 100,000 (World population). Significance The prevalence of epilepsy in the Lecco district was comparable to other studies, whereas the incidence was among the highest. With adjustments, administrative records are a cost-effective instrument to monitor epilepsy frequency. [ABSTRACT FROM AUTHOR]

Background: The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined. Background: The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined. Methods: 174 adult patients with epilepsy with chronic comorbidities, multiple-drug therapy and reporting at least one adverse treatment effect and/or drug interaction at study entry were randomly assigned to the educational plan or usual care. The primary endpoint was the number of patients becoming free from adverse treatment events and/or drug interactions after a 6- month follow-up. The number of adverse treatment events and drug interactions, health-related quality of life (HRQOL) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes. Results: The primary endpoint was met by 44.0% of patients receiving the educational plan versus 28.9% of those on usual care (p=0.0399). The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study: OR (95% CI) of 2.29 (1.03 to 5.09). A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment. Quality of life and costs were not significantly different in the two groups. Conclusions A patient-tailored educational strategy is effective in reducing drug-related problems (particularly drug interactions) in epilepsy patients with chronic comorbidities, without adding significant monetary costs. [ABSTRACT FROM AUTHOR]

Abstract: Misconception and stigma towards epilepsy have a profound impact on this disease in Africa. An unselected sample of Zambian people was interviewed to investigate their knowledge and attitudes towards epilepsy. Proper/improper answers were scored, and a composite score was developed with negative values for unsatisfactory awareness and high stigma levels. The sample comprised 231 people residing in urban (107) or in rural (124) areas. The median and interquartile range of scores for epilepsy awareness and stigma were, respectively, −1 (−3; +1) and +1 (−1; +6). Poor education was the only significant predictor of unsatisfactory awareness (p=0.0131), while education and residency were significantly associated with stigma (p<0.0001 and p=0.0004). Rural people were mostly in the highest stigma level (44.2%) and urban people in the lowest stigma level (60.4%). Misconception and negative attitudes towards epilepsy among Zambian people reflect poor education and rural residency. [Copyright &y& Elsevier]

Abstract: Morphological, stratigraphical and structural investigations integrated with palaeomagnetic and tephrostratigraphic studies and 40Ar/39Ar measurements allowed us to define the Quaternary tectonic–sedimentary evolution of the epicentral area of the L''Aquila 2009 earthquake (Mw 6.3). This area roughly matches the Paganica–San Demetrio–Castelnuovo (PSC) intermountain basin filled by a fluvio-lacustrine succession that is variously deformed by normal faults. At its early stage (Early Pleistocene; ca 2 Ma), the basin hosted a lake that was characterised by whitish carbonate silt and mud deposition. Towards the end of the Early Pleistocene, this was partly filled by a south-eastward prograding deltaic system. The south-easternmost portion of the deltaic system was successively abandoned and eroded, while sedimentation of a braided river system developed in a smaller area westwards. Before 780 ka, this fluvio-lacustrine system (the Lower PSC syntheme) ended, and the area underwent erosional and pedogenic processes. These processes continued up to >460 ka, with the onset of fluvial gravel and volcanic-rich silty sand deposition over a narrow area of the south-western PSC basin (an earlier unit of the Upper PSC syntheme, early Middle Pleistocene). Around 460 ka, when most of this area was again subjected to denudational processes, the sedimentation migrated into the previously exposed north-western area of the PSC basin, where fluvial/alluvial sediments were deposited, between ca 460 ka and ca 350 ka (a later unit of the Upper PSC syntheme). Between ca 350 ka and the present, the sedimentation continued uninterrupted in a slight westwards restricted area of the PSC basin (Upper–Late PSC syntheme). The significant contraction of the basin, the shifting of its depocentre, the variation in its geometry and in the spatial distributions and thicknesses of the units constituting the Lower, Upper and Late PSC synthemes, provide evidence for strong tectonic control. This resulted in progressive reduction of the activity of the south-easternmost tectonic structures and parallel migration of the fault activity on the westernmost structures. In this perspective, the fault system responsible for the L''Aquila 2009 earthquake can be seen as the most recent expression of a long-lasting westwards polarised process of tectonic activity transfer. [Copyright &y& Elsevier]

SUMMARY Urgent urban-planning problems related to the 2009 April, Mw 6.3, L'Aquila earthquake prompted immediate excavation of palaeoseismological trenches across the active faults bordering the Aterno river valley; namely, the Mt. Marine, Mt. Pettino and Paganica faults. Cross-cutting correlations amongst existing and new trenches that were strengthened by radiocarbon ages and archaeological constraints show unambiguously that these three investigated structures have been active since the Last Glacial Maximum period, as seen by the metric offset that affected the whole slope/alluvial sedimentary succession up to the historical deposits. Moreover, in agreement with both 18th century accounts and previous palaeoseismological data, we can affirm now that these faults were responsible for the catastrophic 1703 February 2, earthquake ( Mw 6.7). The data indicate that the Paganica-San Demetrio fault system has ruptured in the past both together with the conterminous Mt. Pettino-Mt. Marine fault system, along more than 30 km and causing an Mw 6.7 earthquake, and on its own, along ca. 19 km, as in the recent 2009 event and in the similar 1461 AD event. This behaviour of the L'Aquila faults has important implications in terms of seismic hazard assessment, while it also casts new light on the ongoing fault linkage processes amongst these L'Aquila faults. [ABSTRACT FROM AUTHOR]

The relation between coffee intake and risk of amyotrophic lateral sclerosis (ALS) was investigated in 377 newly diagnosed ALS patients from 4 Italian population-based registries in the European ALS Consortium (EURALS Group) (2007–2010). For each patient, 2 age- and sex-matched hospital controls were selected, one from a neurology department and one from a nonneurologic department. Two additional healthy control groups were identified from local general practitioners’ (GPs’) lists (n = 99) and residents of the same area as a cancer cohort (n = 7,057). Coffee intake was defined in terms of status (ever consuming coffee daily for ≥6 months vs. never), duration, and history (never, former, or current). Ever coffee drinkers comprised 74.7% of ALS patients, 80.4% of neurologic controls, 85.6% of nonneurologic controls (P = 0.0004), 88.9% of GP controls (P = 0.0038), and 86.0% of cancer cohort controls (P < 0.0001). Current coffee drinkers comprised 60.2% of ALS patients, 70.2% of neurologic controls (P = 0.0294), 76.4% of nonneurologic controls (P < 0.0001), and 82.3% of GP controls (P = 0.0002); duration of intake was ≥30 years for 62.3%, 67.7%, 74.7%, and 72.6%. ALS patients had lower lifetime coffee exposure: Odds ratios were 0.7 (95% confidence interval (CI): 0.5, 1.1), 0.6 (95% CI: 0.4, 0.8), and 0.4 (95% CI: 0.2, 0.9) in comparison with neurologic, nonneurologic, and GP controls, respectively. In current (vs. never) coffee drinkers, odds ratios were 0.7 (95% CI: 0.5, 1.0), 0.5 (95% CI: 0.3, 0.7), and 0.4 (95% CI: 0.2, 0.8), respectively. These findings provide epidemiologic evidence of an inverse correlation between coffee intake and ALS risk. [ABSTRACT FROM PUBLISHER]

Abstract: On 6 April, 2009, a Mw 6.3 earthquake struck L’Aquila and dozens of neighbouring villages (Abruzzo, central Italy) causing 308 deaths and with thousands injured. Within Italian seismicity, this was the strongest event since 1980 (Irpinia; Mw 6.9), and the first located so close to a large city since 1908 (Messina; Mw 7.3). Consistent data from an integrated approach (including stratigraphy, geomorphology, tephrochronology and paleoseismology) have allowed us to identify a 19-km-long, hitherto poorly known structure as being responsible for this earthquake (Paganica–San Demetrio fault system, PSDFS). The fingerprinting of four well-dated tephra layers and a detailed outline of the geomorphological and stratigraphic setting have provided the basis for assessing the behaviour of the PSDFS since its early activity, here dated at least ca 500 ka, to the present. The slip rate of the structure, calculated over different time windows, has fluctuated slightly ca 0.5 mm/yr. Paleoseismological analyses revealed the traces of the last surface-faulting events; thus, we unambiguously recognise the offset associated with the Mw 6.7 earthquake of 1703, which was previously related to other conterminous structures, along with an older comparable strong event, speculatively ascribed to an event purely known as the AD 801 central Apennine earthquake. This study shows that a long-term to short-term integrated approach is crucial in seismic hazard evaluation, especially when dealing with fault systems that are difficult to trace geomorphically, despite being capable of generating 2009-like earthquakes or even stronger events when conterminous structures are also involved. [ABSTRACT FROM AUTHOR]

We investigated the late Upper Pleistocene activity of the eight main faults that comprise the active, dip-slip Gran Sasso fault system (GSFS) in the Gran Sasso d'Italia Massif (central Italian Apennines; 2912 m a.s.l.). We carried out novel paleoseismological analyses at four sites of three different fault segments, and reviewed the data of the previous results for three other segments. We carried out several topographic profiles across the offset hillslopes, alluvial fans, glacial cirques, moraines, and valley floor. Through the dozen radiocarbon datings that were combined and cross-checked with many other ages published in previous studies, we have provided robust slip-rates and reconstructed the Holocene seismic history of this fault system. Paleoseismic analyses revealed the presence of three consecutive earthquakes since the onset of the Late Holocene, which were separated by 3.3 ky and 2.2 ky, respectively. The last one occurred in the 13th–14th century CE, a time-span that fits with the catastrophic 1349 seismic sequence. Our review of the macroseismic intensity distribution of this sequence indicates the existence of two distinct mesoseismic areas; a southern one that was already related to the Aquae Iuliae fault rupture (Abruzzi-Campania-Molise borders), and a northern one that robustly matches the hanging-wall of the Gran Sasso fault system. Given the length of this fault system, we estimated Mw 7 for its entire rupture, which accounts for the total destruction of L'Aquila and the neighboring villages. This also accounts for the strong effects and severe damage suffered by several settlements in the para-Tyrrhenian far field, especially to buildings characterized by long fundamental resonance periods, as seen for the monuments of Rome. Although characterized by long recurrence times (2.8 ± 0.5 ky), our results suggest that as for all of the main silent faults of the eastern set of active structures in the central Apennines, this fault system has one of the largest seismogenic potentials of the whole Apennine chain, with seismic risk implications extended even to its far-field. • Paleoseismic trenching reveals the Holocene seismic history of the Gran Sasso fault. • Coseismic surface rupture length indicates a Mw 7.0 seismogenic potential. • The Gran Sasso fault rupture caused severe damage in Rome in the 1349 earthquake. [ABSTRACT FROM AUTHOR]

Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14-0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10-0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81-0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work. [ABSTRACT FROM AUTHOR]

A multi-proxy record (lithology, XRF, CaCO 3 content, carbonate δ 18 O and δ 13 C) was acquired from a sediment core drilled in the intermountain Sulmona basin (central Italy). Tephrostratigraphic analyses of three volcanic ash layers ascribe the investigated succession to the MIS 12-MIS 11 period, spanning the interval ca. 500–410 ka. Litho-pedo facies assemblage indicates predominant lacustrine deposition, interrupted by a minor sub-aerial and lake low stand episode. Variations in major and minor elements concentrations are related to changes in the clastic input to the lake. The oxygen isotopic composition of carbonate (δ 18 O c ) intervals is interpreted mainly as a proxy for the amount of precipitation in the high-altitude catchment of the karst recharge system. The record shows pronounced hydrological variability at orbital and millennial time-scales, which appears closely related to the Northern Hemisphere summer insolation pattern and replicates North Atlantic and west Mediterranean Sea Surface Temperature (SST) fluctuations. The MIS 12 glacial inception is marked by an abrupt reduction of precipitation, lowering of the lake level and enhanced catchment erosion. A well-defined and isotopically prominent interstadial with increased precipitation maybe related to insolation maxima-precession minima at ca. 465 ka. This interstadial ends abruptly at ca. 457 ka and it is followed by a phase of strong short-term instability. Drastic lake-level lowering and enhanced clastic flux characterized the MIS 12 glacial maximum. Lacustrine deposition restarted about 440 ka ago. The MIS 12–MIS 11 transition is characterized by a rapid increase in the precipitation, lake-level rise and reduction in the clastic input, interrupted by a short and abrupt return to drier conditions. Comparison with marine records from the Iberian margin and western Mediterranean suggests that major events of ice rafted debris deposition, related to southward migrations of the polar front, match the harshest periods in central Italy. This indicates strong teleconnections between Northern hemisphere ice sheet dynamics, North Atlantic oceanic conditions and Mediterranean continental hydrology. [ABSTRACT FROM AUTHOR]

The only available treatment of traumatic spinal cord injury (TSCI) is high-dose methylprednisolone (MP) administered acutely after injury. However, as the efficacy of MP is controversial, we assessed the superiority of erythropoietin (EPO) versus MP in improving clinical outcome of acute TSCI. Patients aged 18 to 65 years after C5-T12 injury, and grade A or B of the ASIA Impairment Scale (AIS), admitted within 8 h, hemodynamically stable, were randomized to MP according to the NASCIS III protocol or EPO iv (500 UI/kg, repeated at 24 and 48 h). Patients were assessed by an investigator blind to treatment assignment at baseline and at day 3, 7, 14, 30, 60 and 90. Primary end point: number of responders (reduction of at least one AIS grade). Secondary end points: treatment safety and the effects of drugs on a number of disability measures. Frequentistic and post hoc Bayesian analyses were performed. Eight patients were randomized to MP and 11 to EPO. Three patients (27.3 %) on EPO and no patients on MP reached the primary end point ( p = 0.17). No significant differences were found for the other disability measures. No adverse events or serious adverse events were reported in both groups. The Bayesian analysis detected a 91.8 % chance of achieving higher success rates on the primary end point with EPO in the intention-to-treat population with a 95 % chance the difference between EPO and MP falling in the range (−0.10, 0.51) and a median value of 0.2. The results of Bayesian analysis favored the experimental treatment. [ABSTRACT FROM AUTHOR]

Objectives To verify the net effect of seizures after stroke on the use of in-hospital health care resources. Methods Consecutive patients with first-ever stroke were admitted to the stroke unit of a Moscow hospital and followed prospectively until death or discharge. Each patient experiencing seizures was matched for age, sex, stroke type, National Institutes of Health Stroke Scale score at admission, and stroke risk factors to 2+ patients with no seizures, as controls. Resources consumed included length of hospital stay, admission to the intensive care unit ( ICU), diagnostic tests, medical consultations and treatments. Cost estimates were based on the Russian National Health Service perspective. Results The sample comprised 30 patients with in-hospital seizures and 70 matched controls. Patients dying in hospital were 15 of 30 (50%) versus 4 of 70 (5.7%) (p < 0.001). The overall cost of hospital stay was only slightly (nonsignificantly) higher in patients with seizures, but the cost was significantly higher in patients who died than in patients who were discharged alive. Compared to the controls, patients with seizures spent more intensive care unit ( ICU) days and required more computed tomography ( CT) scans, x-rays, endoscopies, and specialist consultations, causing higher in-hospital costs. Significance In patients with first-ever stroke, seizures per se do not increase the overall in-hospital costs. However, the higher than expected mortality in patients with seizures is associated with additional hospital costs. [ABSTRACT FROM AUTHOR]

Background: We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. Methods: By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1–60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. Results: Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1–57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7–60). Worsening occurred 1–24 months (median 4.5) after IVIg discontinuation and 1–31 months (median 14) after IVMP discontinuation (p=0.0126). Conclusions: A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP. [ABSTRACT FROM AUTHOR]

Past orbital analogues to the current interglacial, such as Marine Isotope Stage 19c (MIS 19c, ca. 800 ka), can provide reliable reference intervals for evaluating the timing and the duration of the Holocene and factors inherent in its climatic progression. Here we present the first high-resolution paleoclimatic record for MIS 19 anchored to a high-precision 40Ar/39Ar chronology, thus fully independent of any a priori assumptions on the orbital mechanisms underlying the climatic changes. It is based on the oxygen isotope compositions of Italian lake sediments showing orbital- to millennial-scale hydrological variability over the Mediterranean between 810 and 750 ka. Our record indicates that the MIS 19c interglacial lasted 10.8 ± 3.7 k.y., comparable to the time elapsed since the onset of the Holocene, and that the orbital configuration at the time of the following glacial inception was very similar to the present one. By analogy, the current interglacial should be close to its end. However, greenhouse gas concentrations at the time of the MIS 19 glacial inception were significantly lower than those of the late Holocene, suggesting that the current interglacial could have already been prolonged by the progressive increase of the greenhouse gases since 8-6 ka, possibly due to early anthropogenic disturbance of vegetation. [ABSTRACT FROM AUTHOR]

Background: Increased titres of serum IgM antibodies to GM1 ganglioside are often associated with multifocal motor neuropathy (MMN). Testing for IgM antibodies to other antigens including GM2, the mixture of GM1 and galactocerebroside (GM1/GalC) and the disulfated heparin disaccharide NS6S were reported to increase the sensitivity of antibody testing in MMN even if it is unclear whether the specificity and positive (PPV) or negative predictive value (NPV) for MMN were also affected.Methods: We measured IgM antibodies to GM1, GM2, galactocerebroside, GM1/GalC and NS6S in 40 consecutive patients with MMN and 142 controls with other neuropathies or related diseases and compared their sensitivity, specificity and PPV for MMN.Results: With the only exception of anti-GM2 and, partially, anti-NS6S antibodies, IgM antibodies to the antigens tested were more frequent in MMN than in controls. Increased titres of anti-GM1 IgM were found in 48% of MMN patients with a specificity of 93% and PPV for MMN of 66%. Anti-GM1/GalC antibodies were present in all anti-GM1 positive MMN patients and in 11 additional patients (28%) with MMN raising the sensitivity of antibody testing to 75%. The specificity (85%) and PPV (59%) for MMN was, however, moderately reduced compared to anti-GM1 IgM, even if they rose with increasing anti-GM1/GalC titres. IgM antibodies to GM2, NS6S and galactocerebroside were found in 8%, 23% and 60% of MMN patients but had a low specificity and PPV for MMN.Conclusions: Testing for anti-GM1/GalC IgM significantly increased the sensitivity of antibody testing in MMN compared to anti-GM1 alone (p=0.021) and may represent a preferred option for GM1 reactivity testing in MMN. [ABSTRACT FROM AUTHOR]

Background Increased titres of serum IgM antibodies to GM1 ganglioside are often associated with multifocal motor neuropathy (MMN). Testing for IgM antibodies to other antigens including GM2, the mixture of GM1 and galactocerebroside (GM1/GalC) and the disulfated heparin disaccharide NS6S were reported to increase the sensitivity of antibody testing in MMN even if it is unclear whether the specificity and positive (PPV) or negative predictive value (NPV) for MMN were also affected. Methods We measured IgM antibodies to GM1, GM2, galactocerebroside, GM1/GalC and NS6S in 40 consecutive patients with MMN and 142 controls with other neuropathies or related diseases and compared their sensitivity, specificity and PPV for MMN. Results With the only exception of anti-GM2 and, partially, anti-NS6S antibodies, IgM antibodies to the antigens tested were more frequent in MMN than in controls. Increased titres of anti-GM1 IgM were found in 48% of MMN patients with a specificity of 93% and PPV for MMN of 66%. Anti-GM1/GalC antibodies were present in all anti-GM1 positive MMN patients and in 11 additional patients (28%) with MMN raising the sensitivity of antibody testing to 75%. The specificity (85%) and PPV (59%) for MMN was, however, moderately reduced compared to anti-GM1 IgM, even if they rose with increasing anti-GM1/GalC titres. IgM antibodies to GM2, NS6S and galactocerebroside were found in 8%, 23% and 60% of MMN patients but had a low specificity and PPV for MMN. Conclusions Testing for anti-GM1/GalC IgM significantly increased the sensitivity of antibody testing in MMN compared to anti-GM1 alone ( p=0.021) and may represent a preferred option for GM1 reactivity testing in MMN. [ABSTRACT FROM AUTHOR]

Our objective was to assess the effects of acetyl-L-carnitine (ALC) with riluzole on disability and mortality of amyotrophic lateral sclerosis (ALS). Definite/probable ALS patients, 40−70 years of age, duration 6−24 months, self-sufficient (i.e. able to swallow, cut food/handle utensils, and walk), and with forced vital capacity (FVC) > 80% entered a pilot double-blind, placebo-controlled, parallel group trial and were followed for 48 weeks. ALC or placebo 3 g/day was added to riluzole 100 mg/day. Primary endpoint: number of patients no longer self-sufficient. Secondary endpoints: changes in ALSFRS-R, MRC, FVC and McGill Quality of Life (QoL) scores. Analysis was made in the intention-to-treat (ITT) and per-protocol (PP) population, completers and completers/compliers (i.e. taking > 75% of study drug). Forty-two patients received ALC and 40 placebo. In the ITT population, 34 (80.9%) patients receiving ALC and 39 (97.5%) receiving placebo became non-self-sufficient ( p = 0.0296). In the PP analysis, percentages were 84.4 and 100.0% ( p = 0.0538), respectively. Mean ALSFRS-R scores at 48 weeks were 33.6 (SD 10.4) and 27.6 (9.9) ( p = 0.0388), respectively, and mean FVC scores 90.3 (32.6) and 58.6 (31.2) ( p = 0.0158), respectively. Median survival was 45 months (ALC) and 22 months (placebo) ( p = 0.0176). MRC, QoL and adverse events were similar. In conclusion, ALC may be effective, well-tolerated and safe in ALS. A pivotal phase III trial is needed. [ABSTRACT FROM AUTHOR]

Abstract: We describe the diagnostic lithological and chemical features of distal tephras from major Middle-Late Pleistocene (560–36 ka) explosive eruptions of the Colli Albani volcanic district, central Italy. In particular, we explore the time-dependent variability of the Sr and Nd isotope compositions as a tool for recognising and pinpointing individual Colli Albani tephra in distal settings. The distal tephras investigated are in lacustrine and fluvial sediments of central Apennine intermountain basins located 70 km–100 km east of Colli Albani. The recognition of the Colli Albani tephras is essentially based on the K-foiditic composition of their glass, which, within the Italian volcanological framework, is a distinctive character of the Colli Albani pyroclasts. In detail, these tephras are attributed to the following eruptive units: Tufo Pisolitico di Trigoria (561 ± 2 ka); Tufo del Palatino–Tufo di Bagni Albule (530 ± 2/527 ± 2 ka), Tufo di Bagni Albule–Pozzolane Rosse air-fall sequence (517 ± 1 to 500 ± 3 ka), Pozzolane Rosse (457 ± 4 ka), Villa Senni (365 ± 4 ka), and Albano 5–7 (41 ± 7 to 36 ± 1 ka). These correlations are supported by 40Ar/39Ar dating of the distal tephras correlated to the Pozzolane Rosse (457.4 ± 1.7 ka), Villa Senni (365 ± 2 ka) and Albano 5–7 (41 ± 9 ka) and by 87Sr/86Sr measured on clinopyroxene crystals and fresh glassy scoria from distal Colli Albani tephras that range from ∼0.711 to ∼0.709. These ratios are similar to those that characterise the individual proximal correlative units, and show the same decreasing trend over time. In contrast, the 143Nd/144Nd ratios for proximal and distal bulk samples and clinopyroxene increase from ∼0.51212 to ∼0.51215 from the oldest to the youngest tephra deposit. In summary, the study of Sr and Nd isotope compositions that is here applied on products from the Colli Albani volcanic district is a powerful, complementary tool to the more traditional tephrostratigraphic methods (e.g., componentry and electron microprobe analysis) for fingerprinting of distal tephras over a large region of the central Mediterranean, and over a large time interval, such as from 560 ka to 36 ka. [Copyright &y& Elsevier]

Data in the literature show that migraine tends to improve during pregnancy in most migrainous women. The aim of this Internet survey was to obtain the most likely cross section of the situation in the general population with respect to the presence and course of migraine in pregnancy. All women who participated were asked to answer questions pertaining to their history of pregnancy and headache. One thousand and eighteen women participated in the survey; only 775 met the eligibility criteria for inclusion. One hundred and ninety-five women (25.2 %) reported having had a headache only before pregnancy, 425 (54.8 %) before and during pregnancy, and 155 (20.0 %) only during pregnancy. Women suffering from headache before and/or during pregnancy were much more likely to have headaches with more migrainous features at the ID Migraine Screener test when compared to women whose headache began during pregnancy. 'Definite migraines' were 277/620 (44.7 %) and 26/155 (16.8 %), respectively, in the two groups ( p < 0.0001). Among the 620 females that suffered from headache before pregnancy, 375 (60.5 %) improved, 195 (31.5 %) showed complete resolution of the disorder, and 180 (29.0 %) had a reduction in headache frequency. Moreover, the multinomial logistic model (with headache pattern as dependent variable) proved fetal presentation as significant ( p = 0.0042). Women with 'new headache' (No/Yes pattern) had an OR (95 % CI) of 1.9 (1.2-3.0) of breech presentation at delivery versus those with a stable pattern of headache (Yes/Yes). Finally, women with not recent pregnancy stated they suffered from headache less than the women with recent pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: We present new tephrostratigraphic records from the late MIS 5 (ca 110–80 ka) terrestrial sediments from southern and central Italy. On the one hand, the central Italy record consists of an outcropping lacustrine sequence from the Sulmona intermountain basin that contains four trachytic–phonolitic tephra layers (POP3, POP2a, POP2b, POP1), all of which show a K-alkaline affinity that is typical for the Roman co-magmatic Province. The POP3 and POP1 layers were dated by 40Ar/39Ar method at 106.2 ± 1.3 ka (2σ) and 92.4 ± 4.6 ka (2σ), respectively. The sequence in southern Italy, on the other hand, is represented by post-Tyrrhenian coastal deposits of the Cilento area, Campania, which contain two trachytic layers (CIL2, CIL1) that show the same K-alkaline affinity. Based on their chemical compositions and radiometric ages, POP3 and POP1 are firmly correlated with the marine tephra layers X-5 (105 ± 2 ka) and C-22 (ca 90 ka), which, in turn, match tephras TM-25 and TM-23-11, respectively, in the lacustrine sequence of Lago Grande di Monticchio (southern Italy). Of note, the POP1 layer also matches the Adriatic Sea tephra PRAD 2517 that was previously correlated with the older X-5 layer. The tephra couplet POP2a and POP2b (ca 103 and 103.5 ka, extrapolated ages) are compatible with the TM-24b and TM-24-3 tephras in Monticchio, which match both the stratigraphic positions and the chemical compositions. In the Cilento area, as well as the already described X-6 layer (ca 108 ka) (CIL2), we recognise a new stratigraphic superimposed layer (CIL1) that matches the POP3/TM-25/C-27/X-5 Mediterranean marker(s). In summary, the data presented here provide new chemical and 40Ar/39Ar chronological constraints towards a robust late MIS 5 tephrostratigraphy of the central Mediterranean, although at the same time, they also reveal how the tephrostratigraphy itself might be flawed when dealing with tephra markers that are not adequately constrained and characterised. [Copyright &y& Elsevier]

Summary: Background: Intravenous immunoglobulin (IVIg) and corticosteroids are effective as initial treatment in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but little is known about the comparative risk–benefit profile of their long-term use in this disease. We compared the efficacy and tolerability of 6-month therapy with IVIg versus that with intravenous methylprednisolone. Methods: We did a multicentre, randomised, double-blind, placebo controlled, parallel-group study in patients with CIDP. We assessed efficacy and tolerability of IVIg (0·5 g/kg per day for 4 consecutive days) and intravenous methylprednisolone (0·5 g in 250 mL sodium chloride solution per day for 4 consecutive days) given every month for 6 months. Eligible patients had to be in an active or stationary phase of the disease. Allocation to treatment was centrally managed with a computer-generated, 1:1 randomisation scheme with a sequential block size of four. All patients and assessors were unaware of the treatment assignment. After therapy discontinuation, patients were followed up for 6 months to assess relapses. The primary outcome was the difference in the number of patients discontinuing either therapy owing to inefficacy or intolerance. Secondary endpoints included the difference in the proportion of patients experiencing adverse events or worsening after therapy discontinuation. This study is registered with EUDRACT, number 2005-001136-76. Findings: 45 patients (24 IVIg, 21 intravenous methylprednisolone) completed the study; one was excluded for inappropriate inclusion. More patients stopped methylprednisolone (11 [52%] of 21) than IVIg (three [13%] of 24; relative risk 0·54, 95% CI 0·34–0·87; p=0·0085). When adjusted for sex, age, disease duration, comorbidity, modified Rankin scale and ONLS scores at enrolment, and previous treatment with IVIg and steroids, the difference between the two groups remained significant (odds ratio 7·7, 95% CI 1·7–33·9; p=0·0070). Reasons for discontinuation were lack of efficacy (eight in the methylprednisolone group vs three in the IVIg group), adverse events (one in the methylprednisolone group), or voluntary withdrawal (two in the methylprednisolone group). Two patients on IVIg died during follow-up after the 6-month assessment. The proportion of patients with adverse events did not differ between the intravenous methylprednisolone group (14 [67%] of 21) and the IVIg group (11 [46%] of 24; p=0·1606). After therapy discontinuation, more patients on IVIg worsened and required further therapy (eight [38%] of 21) than did those on methylprednisolone (none of ten; p=0·0317). Interpretation: Treatment of CIDP with IVIg for 6 months was less frequently discontinued because of inefficacy, adverse events, or intolerance than was treatment with intravenous methylprednisolone. The longer-term effects of these treatments on the course of CIDP need to be addressed in future studies. Funding: Kedrion. [Copyright &y& Elsevier]

Summary Purpose: Guidelines for refractory epilepsy recommend timely referral of potential surgical candidates to an epilepsy center for evaluation. However, this approach is seldom a priority for treating neurologists, possibly because of inertia of previous practice and personal attitudes, leading to a buildup of psychosocial disabilities and increased risk of morbidity and mortality. The aim of this study was to assess knowledge and attitudes toward epilepsy surgery among practicing neurologists and identify the barriers that delay the treatment. Methods: We surveyed 183 Italian adult and child neurologists with an ad hoc questionnaire exploring physicians' willingness to refer patients for epilepsy surgery when such treatment may be indicated. Thirteen of 14 questions had graded answers ranging from 1 (unfavorable to surgery) to 10 (favorable). We compared the overall scores and per-question scores of the neurologists versus a group of academic and clinical leaders in the field. Key Findings: The neurologists gave responses characterized by extreme variability (i.e., wide response interquartile range) around intermediate scores. Experts had higher and less variable scores favoring surgery. The two groups differed significantly on issues such as how long to pursue pharmacologic treatment and information about indications and outcome of surgery. Multivariate analysis indicated that neurologists' attitudes correlated with the number of patients referred for surgery (p < 0.01) and the geographical region where specialty was attained (p < 0.01). Other variables such as years in practice, number of patients treated for epilepsy, or type of specialty had no predictive value on physicians' behavior. Significance: The majority of Italian neurologists have highly variable attitudes toward epilepsy surgery, reflecting ambivalence and uncertainty toward this type of treatment. About two thirds of responders are nonaligned with the opinion leaders, mainly due to differences in handling pharmacologic treatment and information regarding epilepsy surgery, which affect their attitudes and ultimately patient management. Strategies that may solve the lack of agreement include reinforcing the concept of pharmacoresistance and associated risks, as opposed to the safety and potential benefits of surgery, the use of epilepsy quality measures during follow-up, and the adoption of structured referral sheets and greater involvement of patients in decision making. These measures should facilitate the referral of potential candidates for surgical evaluation and improve overall quality of care. [ABSTRACT FROM AUTHOR]

In the present work we analyse one of the active normal faults affecting the central Apennines, i.e. the Mt. Morrone normal fault system. This tectonic structure, which comprises two parallel, NW-SE trending fault segments, is considered as potentially responsible for earthquakes of magnitude ≥ 6.5 and its last activation probably occurred during the second century AD. Structural observations performed along the fault planes have allowed to define the mainly normal kinematics of the tectonic structure, fitting an approximately N 20° trending extensional deformation. Geological and geomorphological investigations performed along the whole Mt. Morrone south-western slopes permitted us to identify the displacement of alluvial fans, attributed to Middle and Late Pleistocene by means of tephro-stratigraphic analyses and geomorphological correlations with dated lacustrine sequences, along the western fault branch. This allowed to evaluate in 0.4 ± 0.07 mm/year the slip rate of this segment. On the other hand, the lack of synchronous landforms and/or deposits that can be correlated across the eastern fault segment prevented the definition of the slip rate related to this fault branch. Nevertheless, basing on a critical review of the available literature dealing with normal fault systems evolution, we hypothesised a total slip rate of the fault system in the range of 0.4 ± 0.07 to 0.8 ± 0.09 mm/year. Moreover, basing on the length at surface of the Mt. Morrone fault system (i.e. 22-23 km) we estimated the maximum expected magnitude of an earthquake that might originate along this tectonic structure in the order of 6.6-6.7. [ABSTRACT FROM AUTHOR]

Abstract: The Late Pleistocene Albano Maar hosted the most recent volcanic activity of the Colli Albani Volcanic District, represented at near-vent sections by a thick pyroclastic succession of seven units clustered in two main eruptive cycles dated at around 70–68 and 41–36ka B.P., respectively. Recent stratigraphic investigations allowed us to recognise a pyroclastic succession comprising four eruptive units widely spread in the northeastern sectors of the Colli Albani volcano, up to 15km eastward from the Albano Maar. Integrated tephrostratigraphic, morpho-pedostratigraphic, archaeological, petrological and geochemical analyses enable us to recognise them as distal deposits of the first, third, fifth and seventh Albano Maar eruptions, enlarging significantly their previously supposed dispersion area. Further tephrostratigraphic studies in central Apennine area, allowed us to identify the Albano Maar products in Late Pleistocene deposits of several intermountain basins, extending still further the dispersion area of distal ash fallout as far as 100–120km from the vent. On the basis of the identification and the study of these previously unrecognised mid-distal Albano Maar deposits, a reappraisal of the eruptive scenarios and related energetic parameters is proposed. [Copyright &y& Elsevier]

We demonstrate the rational design of nanoporous two-dimensional supramolecular structures by the hierarchical assembly of organic molecules and transition metal atoms at surfaces. Single-molecule level observations with scanning tunneling microscopy monitor the successive aufbau of structures with increasing complexity. From the primary components secondary mononuclear chiral complexes are formed, which represent antecedents for tertiary polynuclear metal-organic nanogrids. These nanogrids represent the constituents of the eventually evolving two-dimensional networks comprising homochiral nanocavity arrays. Our findings visualize the evolution of complex matter in an exemplary way: from per se achiral species via chiral intermediates to mesoscale dissymmetric structures. [ABSTRACT FROM AUTHOR]

This work provides new insights on the use of a combined multidisciplinary approach forestimating trend and rates of valley incision in tectonically active mountainouslandscape. To this aim, here we present the results of a combined analysis includingstream terraces investigation, longitudinal profiles modelling and time-dependent,catchment-scale, geomorphometry obtained in the headwater sector of the Tronto River basin,located in the southern epicentral area of the 2016-2017 seismic sequence of CentralItaly.The most relevant tectonic structures in the area are the Mt. Gorzano fault (south-easternsector), the Sibillini Mts thrust (western sector) and the southern tip of the active Vettorefault, ie the seismogenic structure responsible for the 2016 mainshock. Geomorphometric analysis and stream long-profiles modelling were performed using a 5m-gridded DTM obtained starting from the altimetric dataset included in the 1:5,000topographic maps available for the whole study area in vector format. Time-dependentcatchment-scale R∕Sr metrics and long-profile indices (SL and χ) were computedrespectively using the hydrological tool in ESRI® ArcGIS and the TopoToolboxworking in Matlab®. Stream terraces dataset derives from field survey, integrated withthe visual inspection of a DTM-derived hillshade map and aerial/satellite imageryinterpretations. The combination of R∕Sr time-dependent metrics and stream terraces analysis allows toinfer the timing of the base level changes during upper Quaternary and the long-profilesmodelling provided interesting results for better comprehending the effects of these changeson the fluvial system. The analysis here performed provided new data useful for betterunderstanding the trend and rates of the valley deepening in the headwater sector of theTronto River, to reconstruct basin-scale modifications such as stream captures and, more ingeneral, resulted useful for better comprehending the morphoevolution of this tectonicallyactive key area of the Apennines. Nonetheless, our study did not allow to unravel therole exerted by the single active tectonic structures in the present and past fluvialmorphodynamics, because of the superimposed effects of large gravitational rock slopefailures on the spatial pattern of long-profiles anomalies and local base level variations. [ABSTRACT FROM AUTHOR]

The Mw 6.0 Amatrice earthquake struck central Italy in August 24th 2016, causing hundreds of deaths and injuries, and the almost complete destruction of many historical villages. Unfortunately, the subsequent long-lasting seismic sequence left behind a widespread damage across a wide territory distributed in four Regions. After the emergency period, the Italian Government Commissioner for the reconstruction funded an ambitious project, devoted to the seismic microzonation of 533 urban areas in 138 municipalities, and involving more than 500,000 citizens. The main request of the Government Commissioner was to provide information for urban planning and reconstruction in the municipalities struck by the earthquakes. The project involved several authorities, researchers and freelance consultants, and its scientific coordination was entrusted to the Italian Centre for Seismic Microzonation (CentroMS), an association of 25 research institutions and university departments providing expertise in geology, applied geophysics, engineering-seismology, geotechnical earthquake-engineering, and engineering-geology.The main project activities concerned:• geological surveys and in situ geotechnical testing for the identification of the engineering-geological units;• geophysical surveys for the characterization of the sub-surface units in terms of dynamic properties;• geotechnical laboratory testing for the estimation of the non-linear behavior of the units under cyclic and/or dynamic conditions;• numerical simulations for the estimation of local seismic response (LSR); • seismological analysis for i) retrieval of waveforms compatible with the building code to be used as seismic input for the numerical simulations, ii) calibration of numerical simulations, and iii) empirical determination of LSR.This work presents the main results of the project, aimed at improving the level of knowledge of the territory for reconstruction, and building up the expertise of CentroMS for coordinating future seismic microzonation activities. [ABSTRACT FROM AUTHOR]