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The aim of this work was to start collecting information on rational combination of antibody (Ab) and T cell vaccines into single regimens. Two promising candidate HIV-1 vaccine strategies, sequential isolates of CH505 virus Envs developed for initiation of broadly neutralizing antibody lineages and conserved-mosaic tHIVconsvX immunogens aiming to induce effective cross-clade T cell responses, were combined to assess vaccine interactions. These immunogens were delivered in heterologous vector/modality regimens consisting of non-replicating simian (chimpanzee) adenovirus ChAdOx1 (C), non-replicating poxvirus MVA (M), and adjuvanted protein (P). Outbred CD1-SWISS mice were vaccinated intramuscularly using either parallel CM8M (tHIVconsvX)/CPPP (CH505) or sequential CM16M (tHIVconsvX)/CPPP (CH505) protocols, the latter of which delivered T cell CM prior to the CH505 Env. CM8M (tHIVconsvX) and CPPP or CMMP (CH505) vaccinations alone were included as comparators. The vaccine-elicited HIV-1-specific trimer-binding and neutralizing Abs and CD8+/CD4+ T cell responses induced by the combined and comparator regimens were not statistically separable among regimens. The Ab-lineage immunogen strategy was particularly suited for combined regimens for its likely less potent induction of Env-specific T cell responses relative to homologous epitope-based vaccine strategies. These results inform design of the first rationally combined Ab and T cell vaccine regimens in human volunteers.

Polymer films with optical properties as indicators to thermal stress were obtained through the controlled dispersion of moderate amounts (

SummaryObjectiveTo investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to

SummaryThe aim of the study was to assess sleep-wake habits and disorders and excessive daytime sleepiness (EDS) in an unselected outpatient epilepsy population. Sleep-wake habits and presence of sleep disorders were assessed by means of a clinical interview and a standard questionnaire in 100 consecutive patients with epilepsy and 90 controls. The questionnaire includes three validated instruments: the Epworth Sleepiness Scale (ESS) for EDS, SA-SDQ for sleep apnea (SA), and the Ullanlinna Narcolepsy Scale (UNS) for narcolepsy. Sleep complaints were reported by 30% of epilepsy patients compared to 10% of controls (p=0.001). The average total sleep time was similar in both groups. Insufficient sleep times were suspected in 24% of patients and 33% of controls. Sleep maintenance insomnia was more frequent in epilepsy patients (52% vs. 38%, p=0.06), whereas nightmares (6% vs. 16%, p=0.04) and bruxism (10% vs. 19%, p=0.07) were more frequent in controls. Sleep onset insomnia (34% vs. 28%), EDS (ESS ≥10, 19% vs. 14%), SA (9% vs. 3%), restless legs symptoms (RL-symptoms, 18% vs. 12%) and most parasomnias were similarly frequent in both groups. In a stepwise logistic regression model loud snoring and RL-symptoms were found to be the only independent predictors of EDS in epilepsy patients. In conclusion, sleep-wake habits and the frequency of most sleep disorders are similar in non-selected epilepsy patients as compared to controls. In epilepsy patients, EDS was predicted by a history of loud snoring and RL-symptoms but not by SA or epilepsy-related variables (including type of epilepsy, frequency of seizures, and number of antiepileptic drugs).

Objectives : To appraise the controversial prognostic significance of postanoxic alpha or theta coma (ATC). Methods : We prospectively assessed 14 comatose patients with ATC after cardiac arrest by means of a protocol which included repeated clinical examinations, EEG, and median somatosensory evoked potentials (SEP). Good outcome was defined by the reappearance of cognition (Glasgow outcome scale 3–5) at any time during the 1 year follow-up. Results : Nine of 14 patients had a monotonous, frontally accentuated and areactive alpha (theta) EEG activity (complete ATC). In these patients ATC was recorded a mean of 47 h after resuscitation, the mean Glasgow coma scale (GCS) was 4 at 48 h, and early cortical SEPs were altered or absent in 5 of 7 patients. All nine patients died. In five of 14 patients the alpha (theta) EEG activity was either not monotonous, partially reactive or posteriorly dominant (incomplete ATC). In these patients ATC was recorded a mean of 43 h after resuscitation, the mean GCS was 8 at 48 h, and early cortical SEP were normal in 4 of 5 patients. Three of 5 patients regained cognition, two of them remained however dependent in activities of everyday life. Conclusions : This study and a review 283 cases of postanoxic ATC reported in the literature suggest the existence of incomplete and complete variants of postanoxic ATC. Whereas complete ATC is invariably associated with a poor outcome, full recovery is possible in patients with incomplete ATC. The combination of EEG, clinical, and SEP findings improves the prognostic accuracy of postanoxic ATC.

Summary: Purpose: This study was designed to evaluate the relevance of developmental emotional stress factors, which are considered to influence emotional functioning, as contributing factors in the development of psychogenic symptoms. Methods: Ten patients with nonepileptic seizures (non-ESs) (frequently referred to as psychogenic seizures), in whom diagnosis had been confirmed by a placebo-infusion test (PT), and 10 control patients with complex partial seizures (ESs) were evaluated with regard to developmental background by using structured in-depth interviews performed by a single interviewer blinded to the diagnosis. In addition, outcome assessment in the non-ES group after PT was done. Results: There were no significant differences between groups in developmental psychosocial stress or in any single developmental stress factor. Six months after PT, the outcome was favorable in patients with non-ES: six were seizure free, and two had a considerable reduction in frequency of seizures. Conclusions: Our research indicates the following: (a) a high incidence of developmental stress factors and functional disturbances may be found in patients with non-ESs and ESs; (b) assessment of developmental emotional stress and functional disturbances as a basis for validating the diagonsis of non-ES should be treated with caution; (c) use of PT followed by supportive information about the nonepileptic origin of the attacks may have a positive therapeutic effect or help to introduce psychotherapeutic treatment. Key Words: Psychogenic seizures-Nonepileptic seizures-Developmental emotional stress-Outcome assessment-Placebo-infusion test.

Since published data on the course and prognosis of encephalitis in Central Europe is limited, we retrospectively evaluated 104 children with either acute strict sense encephalitis (n = 80) or acute cerebellar ataxia (n = 24) treated at the Department of Pediatrics, University of Bern, Switzerland, between 1980 and 1991. Of the 80 patients with strict sense encephalitis, four (5%) died acutely and 28 (36%) of 78 followed up had sequelae - eight patients with severe, six with moderate and 14 with mild sequelae. Young age and seizures were shown to correlate with poor outcome. Among the 24 patients with acute cerebellar ataxia, there was no fatal outcome and none developed severe residua, but six had mild and one had moderate sequelae. Initial cerebrospinal fluid white cell count was significantly higher in these children with sequelae compared with those without any sequelae after acute cerebellar ataxia.

Apnoea as an isolated manifestation of seizures is well described in neonates but is only occasionally observed in infants. We present data from four infants, with apnoea as the sole manifestation of seizures, documented by polygraphic ictal electroencephalogram (EEGC) and video recording. The four infants, after normal pregnancy and delivery at term, showed the first apnoea at the age of 2-11 months. The interictal EEG was normal. The ictal EEG and video recording showed in all infants a focal rhythmic alpha or theta activity with or without generalization, which lasted 40-120 seconds. The apnoea appeared a few seconds after the beginning of rhythmic activity and the heart rate remained unchanged during the apnoea. At 2 years' follow-up, three children are seizure-free under anti-epileptic therapy with normal psychomotor development in two, and a slight delay in the third infant. The fourth child has partial seizures and is severely retarded.

The purpose of this study was to determine whether the age at onset of temporal lobe epilepsy influences hippocampal volume. Fifteen right-handed patients with medically intractable partial complex epilepsy of temporal origin were studied in quantified magnetic resonance imaging (MRI) and neuropsychological tests. In seven patients (mean age: 24 years) epilepsy began before the age of three (? YOUNG), in eight patients (mean age: 29 y) after the age of three (= OLDER). Education, social integration, duration of epilepsy and seizure frequency were equal in YOUNG and OLDER. The mean hippocampal volume, after normalization to total intracranial volume was for the right and for the left side smaller in YOUNG than in OLDER (p ≤ 0.02). The side-to-side asymmetry of absolute hippocampal volume was in patients with left-side focus more pronounced in YOUNG than in OLDER (p < 0.03). The number of patients with right-side focus was too small for statistical analysis. Results of neuropsychological testing showed no significant differences between YOUNG and OLDER. Onset-age of epilepsy before three years is associated with a higher risk of bilateral hippocampal hypotrophy and unilateral hippocampal asymmetry. Performance in neuropsychological testing seems not to be significantly influenced by hippocampal volume or age at onset.

The purpose of this study is to identify possible factors which could influence the seizure recurrence after anti-epileptic drug (AED) withdrawal in children with partial epilepsy. AED was discontinued in 82 children who had been free of partial epileptic seizures for 2.0–11.0 years (mean 4.7 years). Twenty-four patients (29.3%) had a relapse from a few days to 6.1 years (mean 1.2 years) after AED discontinuation. Significantly more common in children who relapsed were: younger age at beginning of AED withdrawal, occurrence of complicated febrile convulsions (5/24 vs 1/58,P

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3 months, they were randomized 1:1 to receive atorvastatin 40 mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95 % CI 0.36–3.56; p = 0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p = 0.02). In conclusion, atorvastatin 40 mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month period. Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6513-7) contains supplementary material, which is available to authorized users.

Molecular optical brighteners incorporated into filmable polymers to a very low extent from 0.05 to 0.5 wt.% by melt-processing, provide materials which show a well-defined excimer emission by increasing dye concentration flanked by a characteristic change of the luminescent properties of the films. Then, the original colour of the film, provided by the radiative transitions of the isolated dye molecules, may be restored after polymer stretching that promotes the aggregates break-up and the alignment of the single chromophore molecules along the stretching direction thus providing an easy detectable colour change. The approach can be extended to polymer blends allowing to obtain a wide range of films with different structure and performances in colour changes determined by external stimuli. Also, nanostructured polymer films with unusual and anisotropic optical properties can be obtained through the dispersion of gold and silver nanoparticles. The metal nanoparticles can be produced directly inside the polymer matrix by a photo-reduction process. Both organic chromophores and metal particles nanostructured systems can be used to prepare “smart” coating materials with a broad type of structural characteristics and capable to detect and stores external stimuli of different origin and under different conditions.

In this work, the aggregation behaviour of a chiral perylene derivative, that is, N,N ′-bis-( R )-(1′-phenylethyl)-perylene-3,4,9,10-tetracarboxyldiimide (R-Pery), was studied by means of 1 H NMR (including DOSY techniques), circular dichroism, UV–Vis and fluorescence spectroscopies in various conditions. The acquired data demonstrate that R-Pery tends to aggregate in pure solvents at high concentrations (>10 −5 M in DMSO and >10 −3 M in CHCl 3 ), whereas aggregation occurred at lower concentrations by adding a poor solvent, such as water (to DMSO) or CH 3 CN (to chloroform). Interesting results were obtained studying the optical behaviour of R-Pery when dispersed into a linear low-density polyethylene matrix (LLDPE). In particular, the aggregation extent of R-Pery into LLDPE was investigated by means of UV–Vis, fluorescence and CD spectroscopies as a function of dye concentration as well as thermal stimuli. The optical responsiveness of R-Pery (both in absorption and in emission) versus moderate temperature changes ( i.e. , for T > 35 °C) suggests applications of polymer dispersions as smart and reversible indicators to thermal solicitations.

Linear low density polyethylene (LLDPE) films containing different concentrations of perylene (P) chromophores have been prepared by solution-casting and compression-moulding. The light emission features of the films depend on P concentration and polymer films deformation. A well-defined band attributed to the formation of micro/ nano-structured perylene chromophoric aggregates is observed with more than 0.1 wt.% of P in the film. The occurrence of this phenomenon changed the emission colour of the films from a bright blue (noninteracting dyes) to low intense pale yellow (interacting dyes) colour. During film drawing the LLDPE macromolecules reorganization is able to break the P supramolecular organization, leading to the prevalence of the blue emission of monomeric P. The optical behaviour of perylene dyes acting as internal stressstrain luminescent indicators for polyethylene films, provides a powerful tool to detect macromolecular organization.

In this work, a water soluble perylene derivative containing piperazine peripheral units, i.e. N,N'-bis(2-(1-piperazino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide dichloride (PZPER) was synthesized and dispersed at low loadings (from 0.1 to 1.1 wt%) into vinyl alcohol-containing polymer matrices. From the data acquired, the most effective driving force for the formation of intramolecular aggregates of PZPER was attributed to hydrogen bonding interactions. In particular, the aggregation extent was affected by the reduction of molecular interactions occurring in both solution and in polymer dispersions due to the decreasing polarity of the chromophore environment or increasing temperature. The sensitivity of PZPER aggregates dispersed into vinyl alcohol-containing polymer matrices towards mechanical stress was also reported. The responsiveness of PZPER optical properties (both in absorption and in emission) versus thermal or mechanical solicitations suggests applications of polymer dispersions as smart indicators to external stimuli.

In this work, two perylene derivatives containing different peripheral alkyl chains (i.e., N,N′-bis-(hexyl)- perylene-3,4,9,10-tetracarboxyldiimide (ES-PTCDI) and N,N′-bis-(2′-ethylhexyl)perylene-3,4,9,10-tetracar- boxyldiimide (EE-PTCDI)) were synthesized and efficiently dispersed at low loadings (from 0.01 to 0.1 wt %) into linear low-density polyethylene (LLDPE) by processing in the melt. Spectroscopic investigations (UV-vis and fluorescence) combined with quantum-mechanical studies demonstrated the ability of both chromophores to generate aggregates among the planar structure of dyes when dissolved in solution or dispersed into LLDPE above a certain concentration. The data acquired for dyes’ dispersions into the polymer matrix reveal that the optical properties and responsiveness to mechanical stimuli are strongly dependent on the compactness of perylene aggregates provided by the different molecular structure of dyes. In particular, the strong intermolecular aggregates of ES-PTCDI resulted in being more resistant toward mechanical stress and less orientable by uniaxial drawing along the drawing direction of the film, whereas the less compact and distorted supramolecular architecture of EE-PTCDI chromophores provided composite films with a remarkable optical response to mechanical solicitations.

The authors investigated the effect of oxcarbazepine on cognitive function in children and adolescents (6 to younger than 17 years of age) with newly diagnosed partial seizures in an open-label comparison with standard antiepileptic drug therapy (carbamazepine and valproate). No differences in cognitive tests were observed between oxcarbazepine and carbamazepine/valproate over a 6-month treatment period.

The study describes brain areas involved in medial temporal lobe (mTL) seizures of 12 patients. All patients showed so‐called oro‐alimentary behavior within the first 20 s of clinical seizure manifestation characteristic of mTL seizures. Single photon emission computed tomography (SPECT) images of regional cerebral blood flow (rCBF) were acquired from the patients in ictal and interictal phases and from normal volunteers. Image analysis employed categorical comparisons with statistical parametric mapping and principal component analysis (PCA) to assess functional connectivity. PCA supplemented the findings of the categorical analysis by decomposing the covariance matrix containing images of patients and healthy subjects into distinct component images of independent variance, including areas not identified by the categorical analysis. Two principal components (PCs) discriminated the subject groups: patients with right or left mTL seizures and normal volunteers, indicating distinct neuronal networks implicated by the seizure. Both PCs were correlated with seizure duration, one positively and the other negatively, confirming their physiological significance. The independence of the two PCs yielded a clear clustering of subject groups. The local pattern within the temporal lobe describes critical relay nodes which are the counterpart of oro‐alimentary behavior: (1) right mesial temporal zone and ipsilateral anterior insula in right mTL seizures, and (2) temporal poles on both sides that are densely interconnected by the anterior commissure. Regions remote from the temporal lobe may be related to seizure propagation and include positively and negatively loaded areas. These patterns, the covarying areas of the temporal pole and occipito‐basal visual association cortices, for example, are related to known anatomic paths. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.

Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in focal status epilepticus. The changes on DWI provide am insight into the pathophysiology. We report a 53-year-old man with focal motor status epilepticus involving the left hand, arm and face with focal slowing on EEG. The apparent diffusion coefficients (ADC) were higher in the affected hemisphere than on the other side. At 10 days and 6 weeks after the end of the seizures, we saw normal ADCs and atrophy of the affected hemisphere. We conclude that the MRI findings indicate both cytotoxic and vasogenic oedema during seizure activity and subsequent loss of brain parenchyma.

Drug-resistant epilepsy is an important clinical challenge, both diagnostically and therapeutically. More and more surgical options are being considered, but precise presurgical assessment is necessary. We prospectively studied eight patients with drug-resistant epilepsy, who underwent clinical examination, single photon emission computed tomography (SPECT) and interictal MRI, including diffusion- and perfusion-weighted echoplanar sequences. Lesions suspected on SPECT of being epileptogenic showed mild hypoperfusion, while the diffusion-weighted MRI (DWI) revealed increased apparent diffusion coefficients relative to the other side. However, these abnormalities were not visible on the corresponding maps. We showed that DWI and perfusion-weighted MRI could be used confirm the characteristics and site of an epileptogenic area in patients with drug-resistant epilepsy.

The authors report the clinical, EEG, and SPECT findings of a patient with nocturnal paroxysmal dystonia. Ictal and interictal scalp EEG showed epileptiform activity over both frontal lobes. Subtraction ictal SPECT co-registered to MRI indicated a bilateral significant hyperperfusion in the anterior part of the cingulate gyrus. These results support earlier electrophysiologic investigations by others suggesting that anterior cingulate epilepsy may manifest as nocturnal paroxysmal dystonia, and illustrate the usefulness of computer-assisted SPECT analysis.

The relationship between phototherapy and changes in the cerebral circulation was studied in 50 jaundiced newborn infants. The aim of the study was to determine whether important alterations in cerebral hemodynamic occur under blue light therapy. Blood flow velocity, i.e., the pulsatility index (PI) and the area under the velocity curve (AUVC), was measured in the anterior cerebral arteries (ACA) using a Duplex scan technique. No prominent changes compromise flow in the ACA. PI and AUVC values were similar during and after phototherapy (p greater than 0.5) suggesting effective cerebral autoregulation in term infants undergoing light treatment for hyperbilirubinemia.

The aim of this study was to recognize the possible psychological advantages when children with a severe CNS disorder like myelomeningocele (MMC) are given very early rehabilitation treatment. One hundred and seven newborns with MMC seen between 1971-1992 were prospectively analysed with respect to two different therapeutic approaches. The children born during the period 1971-1980 did not receive very early therapeutic rehabilitation treatment, whereas those born during the period 1981-1992, received this treatment. In the latter group, special attention was paid to support an improvement in the difficult relationship between the parents and the child with MMC as well as between parents and caregivers. The following statistically significant differences between the two treatment programmes were found: (1) all children achieved independent locomotion at 5 years, in the very early intervention group, compared to only 35% (P < 0.001) in the group without this programme. Orthopaedic operations in the first-mentioned group were markedly reduced; (2) urological surgery decreased drastically in the group with very early urodynamic rehabilitation. Thus, there were 0.6 operations per patient in the older group, but only 0.06 operations per patient in the younger one (P < 0.001); (3) normal schooling was reached by 76% (22/29) and social continence by 80% (23/29) of the children with very early interventional therapy. In the older group only 54% reached normal schooling (P < 0.05) and 29% social continence (P < 0.001). The very early co-ordinated medical and physiotherapeutic rehabilitation treatment of children with MMC usually reduces the psychosocial stress and improves the quality of life of these children and of their families.

Sleepwalking is a dissociation between body sleep and mind sleep. We report single photon emission computed tomography (SPECT) in a man with a history of sleepwalking. Our findings suggest that this dissociation arises from activation of thalamocingulate pathways and persisting deactivation of other thalamocortical arousal systems.

L'articolo si propone di indagare il problema della fonte competente a disciplinare la par condicio a livello regionale. In particolare ci si interroga sulla possibilità di un intervento regionale per la disciplina della materia. L'indagine si è estesa alle soluzioni della dottrina, della giurisprudenza e del diritto positivo ma la conclusione pone l'accento sulla mancanza di qualunque intervento in materia da parte delle Regioni.

The contribution deals with constitutional principles, rules, and case law on the "normative impact" of decisions of Constitutional Court as a "factor" that is taken into account in judicial review of legislation.

Il contributo descrive l'assetto dei servizi pubblici locali a seguito dei recenti interventi di riforma, con l'obiettivo di verificare in che modo l'affermazione in via legislativa del principio di concorrenza per l'affidamento del servizio pubblico locale sia in concreto perseguita ed evidenziando le incongruenze e le contraddizione dei molteplici tentativi di riforma del settore susseguitisi a partire dal 2001 fino ad oggi.