Both trait-neutrality and filtering effects are validated by the vegetation patterns detected in the functional recovery of sand grasslands.

Neutral theory of species assembly means that species assembly is governed by stochastic dispersal processes and fluctuations in established populations. An alternative theory suggests that assembly is strongly determined by functional trait filtering governed by abiotic and biotic filtering selecting species from the local species pool. To test these assumptions, in the current paper we analysed vegetation changes in the first 12 years of succession after heavy goose grazing on acidic sand. With trait-based analyses using permanent plots we addressed the following hypotheses: (i) High fluctuations in the trait values are typical in the first years; later a temporally divergent change in the trait patterns of sites with different vertical position became characteristic. (ii) In the functional diversity of regenerative and vegetative traits we expected different temporal patterns. We confirmed the first hypothesis, as in the first few years most traits displayed high fluctuations with no clear patterns. Our findings weakly supported the second hypothesis; while there were distinct patterns detected in the functional richness of traits, functional divergence and evenness displayed no clear distinctive patterns. We can conclude that both trait neutrality and filtering effects operate in the vegetation changes of the first period of secondary succession.

Thermoluminescence characterization of Ag-doped Li2 B4 O7 single crystal materials.

In this study, the thermoluminescence (TL) characteristics of Ag-doped and undoped lithium tetraborate (Li2 B4 O7 , LTB) materials, grown using the Czochralski method, were reported. The TL properties of LTB:Ag, such as glow curve structure, dose response, fading and reproducibility, were investigated. The glow curve of the Li2 B4 O7 :Ag single crystal consists of four peaks located at approximately 75, 130, 190 and 275°C; in undoped LTB, the single crystal shows a broad glow curve with peaks at 65, 90, 125, 160 and 190°C using a heating rate of 5°C/s in the 50-350°C temperature region. The high temperature peak of Ag-doped sample at 275°C has a nonlinear dose response within the range from 33 mGy to 9 Gy. There is a linear response in the range of 33-800 mGy; after which, a sublinear region appears up to 9 Gy for Ag-doped LTB single crystal. For undoped single crystal, the dose response is supralinear for low doses and linear for the region between 1 and 9 Gy. The thermal fading ratio of the undoped material is almost 60% for the high temperature peak after 7 days. Ag-doped LTB single crystal exhibits different behaviour over a period of 7 days.

Study of the compressibility of chewing gum and its applicability as an oral drug delivery system.

Medicated chewing gum tablets were prepared and evaluated as an oral drug delivery system. The morphology and surface free energy of the components were characterized, and the tablets were prepared by direct compression with an instrumented eccentric tableting machine. The compressibility, the porosity and the texture of the tablets were investigated and the dissolution of the active pharmaceutical ingredient (caffeine) from them was tested with a specially-developed method. Cafosa gum base is a co-processed product which is compressible. Because of the sticking of the tablets to the punches and the high friction that arises during ejection from the die, the use of lubricants and suitable (e.g. Teflon-coated) punches is necessary on a production scale. For this purpose, magnesium stearate with high specific surface area was applied. The release of caffeine in response to the mechanical effect applied proved to be rapid and quantitative and the profile closely obeyed the Korsmeyer-Peppas equation, which is valid in the case of matrix systems. Medicated chewing gum tablets can be used as matrix tablets for oral pharmaceutical administration.

Long-term adjunctive lacosamide treatment in patients with partial-onset seizures.

OBJECTIVE: To evaluate long-term (up to 5.5 years) safety, seizure reduction, and maintenance of efficacy of the antiepileptic drug (AED) lacosamide as adjunctive treatment in an open-label extension trial (SP774; ClinicalTrials.gov: NCT00515619). METHODS: Three hundred and seventy-six adults with partial-onset seizures taking 1-3 AEDs enrolled following completion of a double-blind trial of adjunctive lacosamide. During open-label treatment, dosage of lacosamide (100-800 mg/day) and/or concomitant AEDs could be adjusted to optimize tolerability and seizure control. RESULTS: Kaplan-Meier estimates of patient retention were 74.5% at 12 months, 52.9% at 36 months, and 40.6% at 60 months; median open-label treatment duration was 1183 days (~3.2 years). The most frequently reported treatment-emergent adverse events were dizziness (24.2%), headache (14.4%), diplopia (13.8%), and nasopharyngitis (13.8%); 9.0% of patients discontinued due to adverse events, most commonly dizziness (1.3%). Median percent reduction in 28-day seizure frequency from baseline of the double-blind trial was 49.9% overall, 55.4% for 1-year completers, and 62.3% for 3-year completers. Overall, 50.0% of patients were considered ≥50% responders (achieved ≥50% reduction in 28-day seizure frequency); 55.9% of 1-year completers and 63.0% of 3-year completers were ≥50% responders. CONCLUSION: In eligible patients who entered the open-label extension trial, lacosamide was generally well tolerated. For most patients within each yearly completer cohort, seizure reduction was maintained over time.

LGI Proteins and Epilepsy in Human and Animals.

Leucine-rich glioma-inactivated (LGI) protein was first thought to have a suppressor effect in the formation of some cancers. Developments in physiology and medicine made it possible to characterize the function of the LGI protein family and its crucial role in different conditions more precisely. These proteins play an important role in synaptic transmission, and dysfunction may cause hyperexcitability. Genetic mutation of LGI1 was confirmed to be the cause of autosomal dominant lateral temporal lobe epilepsy in humans. The LGI2 mutation was identified in benign familial juvenile epilepsy in Lagotto Romagnolo (LR) dogs. Cats with familial spontaneous temporal lobe epilepsy have been reported, and the etiology might be associated with LGI protein family dysfunction. In addition, an autoimmune reaction against LGI1 was detected in humans and cats with limbic encephalitis. These advances prompted a review of LGI protein function and its role in different seizure disorders.

Origin and compensation of imaging artefacts in localization-based super-resolution microscopy.

Interpretation of high resolution images provided by localization-based microscopy techniques is a challenge due to imaging artefacts that can be categorized by their origin. They can be introduced by the optical system, by the studied sample or by the applied algorithms. Some artefacts can be eliminated via precise calibration procedures, others can be reduced only below a certain value. Images studied both theoretically and experimentally are qualified either by pattern specific metrics or by a more general metric based on fluorescence correlation spectroscopy.

Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders.

Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.

Formulation study of directly compressible chewable polymers containing ascorbic acid.

The topic of this article is the compression physics of different gum bases which can be used to prepare chewing gum tablets by direct compression. Three different gum bases, Pharmagum(®) C, M and S, were tested alone and in different combinations. The preparations were compressed with a Korsch EK0 eccentric tableting machine at compression forces of 5, 7.5, 10, 12.5 and 15 kN. The compression and breaking processes and the physical parameters of the tablets were investigated. The results revealed that increase of the compression force did not significantly change the studied parameters of the tablets.

Clinical, radiological and genetic aspects of leukodystrophies.

The authors summarize the pathomechanism of the myelination process, the clinical, radiological and the genetical aspects of the leukodystrophies, as in 18q deletion syndrome, adrenoleukodysrtophy, metachromatic leukodystrophy, Pelizaeus-Merzbacher leukodystrophy, Alexander disease and olivo-ponto-cerebellar atrophy (OPCA).

Early vegetation development after grassland restoration by sowing low-diversity seed mixtures in former sunflower and cereal fields.

We studied the early vegetation dynamics in former croplands (sunflower and cereal fields) sown with a low-diversity seed mixture (composed of 2 native grass species) in Egyek-Pusztakócs, Hortobágy National Park, East-Hungary. The percentage cover of vascular plants was recorded in 4 permanent plots per field on 7 restored fields between 2006 and 2009. Ten aboveground biomass samples per field were also collected in June in each year. We addressed two questions: (i) How do seed sowing and annual mowing affect the species richness, biomass and cover of weeds? (ii) How fast does the cover of sown grasses develop after seed sowing? Weedy species were characteristic in the first year after sowing. In the second and third year their cover and species richness decreased. From the second year onwards the cover of perennial grasses increased. Spontaneously immigrating species characteristic to the reference grasslands were also detected with low cover scores. Short-lived weeds were suppressed as their cover and biomass significantly decreased during the study. The amount of litter and sown grass biomass increased progressively. However, perennial weed cover, especially the cover of Cirsium arvense increased substantially. Our results suggest that grassland vegetation can be recovered by sowing low diversity mixtures followed up by yearly mowing. Suppression of perennial weed cover needs more frequent mowing (multiple times a year) or grazing.

Electrode manipulation automatism during temporal lobe seizures.

OBJECTIVE: To describe clinical characteristics and lateralizing value of peri-ictal electrode manipulation automatism (EMA) in patients with temporal lobe epilepsy (TLE) and compare our data with ictal manual automatisms described in the literature. METHODS: Two-hundred and five videotaped seizures of 55 consecutive patients with refractory TLE and postoperatively seizure-free outcome were analyzed and EMA (tugging, scratching or adjusting the electrodes and cables) were monitored. RESULTS: Twenty-eight (51%) patients showed EMA during 47 (23%) seizures. Ictal start was noted in 22 seizures and in 19/22 cases EMA finished before the end of seizure. Ictal EMAs were always associated with automotor seizure components. During 25 seizures, exclusively postictal EMAs were observed. Electrode manipulation was presented during 24/112 left-sided and 23/93 right-sided seizures (p = 0.742). Peri-ictal EMA was unilateral (completed by one hand) in 24/47 seizures (10 ictal, 14 postictal); it was done by the hand ipsilateral to the seizure onset zone in 17/24 and by contralateral hand in 7/24 cases (p = 0.064). We observed concomitant contralateral dystonic posturing during 3/10 seizures with unilateral ictal EMA. Unilateral hand automatism, temporally independent from the EMA appeared in 30 (64%) of the 47 seizures. CONCLUSION: Peri-ictal EMA is a frequent phenomenon but shows no lateralizing value in TLE. The mechanism of EMA is in many ways dissimilar from that of earlier described manual automatisms.

Lateralizing value of postictal automatisms in temporal lobe epilepsy.

PURPOSE: To describe clinical characteristics and lateralizing value of postictal automatisms in patients with temporal lobe epilepsy (TLE). METHODS: One hundred and ninety-three videotaped seizures of 55 consecutive patients with refractory TLE and postoperatively seizure-free outcome were analyzed. Ictal as well as postictal (manual, oral and speech) automatisms were monitored. RESULTS: Thirty-four (62%) of the 55 patients showed PA at least once during their seizures. Postictal automatism was observed in 70 (36%) attacks as manual (21%), oral (13%) or speech (9%) automatisms. Fifteen seizures contained a combination of two different postictal automatisms. The presence of postictal oral automatisms did not lateralize the seizure onset zone (p=0.834). Speech automatisms (repetitive verbal behavior) occurred more frequently after left-sided seizures (p=0.002). Postictal unilateral manual automatism showed no lateralizing value occurring by the ipsilateral hand in 10 and the contralateral upper limb in 6 seizures (p=0.454). CONCLUSION: : Postictal automatism is a relatively frequent phenomenon in TLE. Postictal speech automatism lateralizes the seizure onset zone to the left hemisphere. Our observation can help the presurgical evaluation of TLE because verbal perseveration frequently occurs spontaneously, even in seizures without appropriate postictal language testing.

Intentional seizure interruption may decrease the seizure frequency in drug-resistant temporal lobe epilepsy.

We investigated the nature of preictal subjective phenomena and whether they had any effect on the seizure frequency in 95 adult patients with medial temporal lobe epilepsy. Seventy-three (77%) patients indicated that they experienced seizure-provoking factors. Ten patients (11%) had prodromas independent of auras, while auras occurred in 89%. Forty-four patients (46%) reported that that they had tried to stop their seizures in the presence of prodroma or aura and this action had resulted in success at least once. Twenty-one patients (22%) regularly tried to stop their seizures because this effort was often successful according to their interpretation. Patients who reported that they could frequently inhibit their seizures had 1.8 +/- 1.6 seizures/month, a significantly lower mean seizure frequency than those 74 patients who did not do it regularly (4.6 +/- 4.8 seizures/month, P<0.001). Patients who reported regular experience in inhibiting intentionally their seizures more often had affective (P=0.05) and vertiginous auras (P<0.01) as well as isolated auras (P<0.05). Patients who experienced provoking factors showed the same seizure frequency as those who did not. Our results suggest that intentional seizure inhibition had an impact on the severity of drug-resistant epilepsy.

Mosaic mutations of the LIS1 gene cause subcortical band heterotopia.

BACKGROUND: Subcortical band heterotopia (SBH) is a neuronal migration disorder. DCX mutations are responsible for almost all familial cases, 80% of sporadic female cases, and 25% of sporadic male cases of SBH, and are associated with more severe gyral and migration abnormality over the anterior brain regions. Somatic mosaicism has previously been hypothesized in a patient with posteriorly predominant SBH and a mutation of the LIS1 gene, which is usually mutated in patients with severe lissencephaly. The authors identified mosaic mutations of LIS1 in two patients (Patients 1 and 2) with predominantly posterior SBH. METHODS: After ruling out DCX mutations, the authors performed sequencing of the LIS1 gene in lymphocyte DNA. Because sequence peaks in both patients were suggestive of mosaic mutations, they followed up with denaturing high-pressure liquid chromatography analysis on blood and hair root DNA and compared the areas of heteroduplex and homoduplex peaks. A third patient showing the same mutation as Patient 2 but with no evidence of mosaicism was used for comparing the phenotype of mosaic vs full mutation. RESULTS: The two patients with posterior SBH harbored a missense (Arg241Pro) and a nonsense (R8X) mosaic mutation of LIS1. The rate of mosaicism in Patient 1 was 18% in the blood and 21% in the hair roots, whereas in Patient 2 it was 24% and 31% in the same tissues. The patient with a full R8X mutation of LIS1 had severe lissencephaly. CONCLUSIONS: Subcortical band heterotopia can occur with mosaic mutations of the LIS1 gene. Mutation analysis of LIS1, using highly sensitive techniques such as denaturing high-pressure liquid chromatography, should be considered for patients with posteriorly predominant subcortical band heterotopia and pachygyria.

Thermoluminescent and dosimetric properties of X ray phosphors.

Rare earth doped oxide, phosphate, etc. are radioluminescent phosphors that have a broad application in X ray imaging, in luminescent screens, image transformers and in fluorescent lamp manufacturing. Some of them have interesting thermoluminescence features as well, which makes the phosphors applicable also in dosimetry. Two of these materials are Sr3(PO4)2 and BaFCl activated with europium. The general radioluminescence (RL) and thermoluminescence (TL) characteristics of these materials was investigated earlier and the preliminary results have already been published elsewhere. The aim of the present work is to investigate the interesting properties of these phosphors mainly from a dosimetric point of view (sensitivity, dose dependence, etc.).

Aicardi-Goutières syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21.

We have studied 23 children from 13 families with a clinical diagnosis of Aicardi-Goutières syndrome. Affected individuals had developed an early-onset progressive encephalopathy that was characterized by a normal head circumference at birth, basal ganglia calcification, negative viral studies, and abnormalities of cerebrospinal fluid comprising either raised white cell counts and/or raised levels of interferon-alpha. By means of genomewide linkage analysis, a maximum-heterogeneity LOD score of 5.28 was reached at marker D3S3563, with alpha=.48, where alpha is the proportion of families showing linkage. Our data suggest the existence of locus heterogeneity in Aicardi-Goutières syndrome and highlight potential difficulties in the differentiation of this condition from pseudo-TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus types 1 and 2) syndrome.

Elastic model-based segmentation of 3-D neuroradiological data sets.

This paper presents a new technique for the automatic model-based segmentation of three-dimensional (3-D) objects from volumetric image data. The development closely follows the seminal work of Taylor and Cootes on active shape models, but is based on a hierarchical parametric object description rather than a point distribution model. The segmentation system includes both the building of statistical models and the automatic segmentation of new image data sets via a restricted elastic deformation of shape models. Geometric models are derived from a sample set of image data which have been segmented by experts. The surfaces of these binary objects are converted into parametric surface representations, which are normalized to get an invariant object-centered coordinate system. Surface representations are expanded into series of spherical harmonics which provide parametric descriptions of object shapes. It is shown that invariant object surface parametrization provides a good approximation to automatically determine object homology in terms of sets of corresponding sets of surface points. Gray-level information near object boundaries is represented by 1-D intensity profiles normal to the surface. Considering automatic segmentation of brain structures as our driving application, our choice of coordinates for object alignment was the well-accepted stereotactic coordinate system. Major variation of object shapes around the mean shape, also referred to as shape eigenmodes, are calculated in shape parameter space rather than the feature space of point coordinates. Segmentation makes use of the object shape statistics by restricting possible elastic deformations into the range of the training shapes. The mean shapes are initialized in a new data set by specifying the landmarks of the stereotactic coordinate system. The model elastically deforms, driven by the displacement forces across the object's surface, which are generated by matching local intensity profiles. Elastic deformations are limited by setting bounds for the maximum variations in eigenmode space. The technique has been applied to automatically segment left and right hippocampus, thalamus, putamen, and globus pallidus from volumetric magnetic resonance scans taken from schizophrenia studies. The results have been validated by comparison of automatic segmentation with the results obtained by interactive expert segmentation.

[Specific antiepileptic therapy in childhood]. / Specificnosti antiepilepticne terapije u razvojnom dobu.

INTRODUCTION: This paper deals with basic rational antiepileptic therapeutic procedures in children with special consideration of numerous specificities which occur in childhood: difficulties in establishing correct syndrome diagnosis, predominantly after the first or first few seizures which makes it difficult to decide about appropriate syndrome-specific therapy in regard to efficacy, mechanism of action and range of antiepileptic action; difficulties in assessment of subjective factors (their adverse effects and recognition of seizures with subjective symptoms), children's vulnerability in regard to drug toxicity; age-specific pharmacokinetics of these drugs. MATERIAL AND METHODS: The number of available antiepileptics today is great due to new drugs, but carbamazepine (CBZ) and valproate (VAL) are still basic antiepileptics, although carbamazepine's action is reduced to partial epilepsies. The paper describes range of action of available antiepileptics in regard to classification of epileptic seizures and most frequent epileptic syndromes. DISCUSSION: Adverse effects of antiepileptic agents depend on the age, so examples of age-dependent adverse effects are given considering conventional and new antiepileptics. It is well known that optimal control of seizures depends not only on correct choice of drug, but also on appropriate dosage; it is necessary to be informed about age-dependent characteristics of clinical pharmacokinetics: resorption, metabolism, elimination and half-life of antiepileptics. Although 70-80% of children may be well treated with monotherapy, 15% of children require combination of 2 or more drugs causing drug interactions in resorption, distribution, metabolism and elimination. Examples of antiepileptic interactions as well as interactions of other drugs and antiepileptics are given. The paper also deals with special importance of the psychosocial aspects of epilepsy. These children are often unaccepted by others, mostly because others are afraid of their disease, which contributes to poor quality of life of these children. Development of intellectual, emotional functions, physical development and socialization, apart from affecting the choice of drug, make epilepsy treatment in children more complex, with special emphasis on mental-hygienic aspects of complete management of children. CONCLUSION: Only a complex approach to child suffering from epilepsy may provide optimal development, quality of life improvement and complete social integration. Rational therapy of epilepsy in children requires good knowledge not only of age-specific syndromes, clinical pharmacology of anticonvulsants, their efficacy and range of action, but also specificity of their metabolism in children, profile of adverse effects as well as facing numerous nonmedical problems.

[Occurrence, causes and clinical characteristics of status epilepsy in adults]. / Ucestalost, uzroci i klinicke karakteristike epilepticnog statusa kod odraslih.

INTRODUCTION: Status epilepticus, particularly grand mal, is one of the gravest and most dramatic conditions in neurology requiring immediate attention. Status epilepticus can occur in epileptic patients, often with higher mortality rates in symptomatic than idiopathic, but also as an initial symptom of a number of neurological and systemic diseases. No data are available on the exact incidence rates of status epilepticus. According to some assessments, 10% of patients have at least one status epilepticus in their lifetime (3,6). The prognosis mostly depends on the main cause, time in which seizures are stopped and age of patients. Latest data available in literature suggest the mortality rate of 2-8%. MATERIALS AND METHODS: We analyzed frequency of hospital admissions, causes and clinical characteristics of status epilepticus in adults. The study was retrospective, based on case histories of epileptic patients from the Intensive Care Unit of the Neurology Clinic in Novi Sad in 1990, 1993 and 1995. Special emphasis was placed on differences in studied parameters between cases confirmed earlier and those with status epilepticus occurring as an initial symptom of some other illness or condition. RESULTS: Number of hospital admissions rose slightly in the interval observed in comparison with total admissions (0.68% in 1990, 1.24% in 1993, and 1.73% in 1995) (Tabs 1 and 2). During 1993, status epilepticus was more frequent in cases confirmed earlier (69%) compared with the years 1990 (56%) and 1995 (43%) (Graf.1). Epileptic patients were younger on the average than nonepileptic ones (Tab. 3). Status epilepticus occurred more often in male patients (Tab. 4). Irregular treatment was the prevailing cause in epileptic patients (Tab 5). Symptomatic status epilepticus was reported higher in 1990 and 1995, and stroke was definitely the predominant cause (Tab 6). Convulsive grand mal status prevailed in all patients (Graf 2). Focal status was a more frequent finding in nonepileptic patients (Graf 3). Every third in 16 patients died in 1993 and every fifth in 23 in 1995 probably due to the acute destructive brain damage rather than the status itself. No deaths occurred in 1990. DISCUSSION: According to research carried out by other authors, half of grand mal status cases occurred in confirmed epileptics (4). In our study the grand mal status was reported in 70.4% cases of epilepsy. Primary cause was abrupt withdrawal of antiepileptic treatment, infections, alcohol abuse and use of convulsive drugs. This is compatible with our results which confirm that grand mal status either primary or with secondary generalization prevail in both groups of patients (7,8,9). In terms of causes of status epilepticus in nonepileptic patients, literature data mainly suggest cerebral trauma, frontal brain tumors, cerebral arteriosclerosis or other vascular disorders and anaphylaxis (4). Our results point to stroke as the major cause of status epilepticus in nonepileptic patients, similar with data presented by Towne (10). There is no data in literature concerning the relation between sex of patients and occurrence of status. In our study status epilepticus occurred more frequently in male patients. CONCLUSION: The grand mal status was the major clinical type of status in all patients and was primarily caused by discontinued or irregular antiepileptic treatment in patients with confirmed epilepsy, and by stroke in nonepileptic patients.