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Regional groundwater models used for analyzing groundwater systems (infiltration-discharge relations) are often steady state and, therefore, need long-term average recharge input. On the other hand, the spatial variation in the recharge due to distributed land-use, soil type or texture, slope, groundwater level, meteorological conditions, etc., can be significant and should, therefore, be taken into account. Hence, WetSpass was developed as a physically-based methodology for estimation of long-term average spatial patterns of surface runoff, actual evapotranspiration, and groundwater recharge. The model is especially suitable for studying effects of land-use changes on the water regime in a basin. The computer model was integrated in the GIS ArcView. Its set-up is extremely flexible; it allows easy new definition of natural or man-made land-use types. This paper describes the concept of the model and gives an example of a developed WetSpass recharge map for the Gaza Strip, Palestine. [ABSTRACT FROM AUTHOR]

The spatially distributed hydrologic model WetSpa working on a daily or hourly time scale combines elevation, soil and landuse data within GIS, to predict flood hydrographs and spatial distribution of hydrologic characteristics in a watershed. The model is applied to the Margecany-Hornad river basin (1,131 km2) located in Slovakia. Daily hydrometeorological data from 1991 to 2000, including precipitation data from nine stations, temperature data from four stations and evaporation data measured at one station are used as input to the model. Three base maps, i.e., DEM, landuse and soil types are prepared in GIS form, using 100×100 m cell size. Results of the simulations show good agreement between calculated and measured hydrographs at the outlet of the basin. The model predicts the daily/hourly hydrographs with good accuracy, between 75-80% according to the Nash-Sutcliff criteria. For assessing the impact of forests on floods, the calibrated model is applied for a reforestation scenario using the hourly data of the summer of 2001. The scenario considers a 50% increase of forest areas. The model results show that the reforestation scenario decreases the peak discharge by 12%. Investigation of peak discharges from the whole simulation period, shows that the scenario results are reduced by 18% on average. Also, the time to peak of the simulated hydrograph of the reforestation scenario is 14 h longer than for the present landuse. The results show that the effect of land cover on flood is strongly related to storm characteristics and antecedent soil moisture. [ABSTRACT FROM AUTHOR]

A spatially distributed hydrologic model (WetSpa) is used to estimate daily river water discharge in the Simiyu river a tributary of Lake Victoria, Tanzania. The model combines topography, landuse and soil maps, and observed daily meteorological time series to predict discharge hydrographs and the spatial distribution of hydrological parameters in the catchment. The elevations in the catchment range from 2000 to 1100m at the outlet, with average slope of 1.4%. The dominant landuse types are, wasteland, grassland, bushland, cultivated land, and a very small area is covered by surface water. The dominant soil types are sandy loam, followed by sandy clay loam, clay loam, clay, loam and sandy clay. There are two distinctive seasons in the Simiyu catchment. Short rains mainly in November, December and January, and long rains in March to May, resulting in a total average annual precipitation of 700 to 1000 mm. The annual potential evapotranspiration is about 1300 mm, and the river discharge at the catchment outlet ranges from 0 to about 200m³/s. Global parameters of the model are calibrated using three years of daily observed discharge values measured at the mouth of the river at Lake Victoria. The estimated average travel time of the runoff to the outlet of the catchment is about 2.4 d and maximum 8 d for the most remote areas. The model results also show that the surface runoff and interflow provide respectively 38.6% and 61.4% of the total runoff, while the contribution of groundwater drainage is nil. The absence of groundwater drainage is probably due to the high evaporation demand of the atmosphere, which accounts for about 90% of the total precipitation being lost by evapotranspiration. The annual water balance estimated with the model reveals that the total outflow to Lake Victoria is about 500x106m³ per year, which occurs mainly in the wet seasons, i.e. from March to May and from November to January. The volume of runoff produced by agricultural land amounts to about 9% of the total runoff annually. [ABSTRACT FROM AUTHOR]

The major obstacles for modelling flood processes in karst areas are a lack of understanding and model representations of the distinctive features and processes associated with runoff generation and often a paucity of field data. In this study, a distributed flood-modelling approach, WetSpa, is modified and applied to simulate the hydrological features and processes in the karst Suoimuoi catchment in northwest Vietnam. With input of topography, land use and soil types in a GIS format, the model is calibrated based on 15 months of hourly meteorological and hydrological data, and is used to simulate both fast surface and conduit flows, and groundwater discharges from karst and non-karst aquifers. Considerable variability in the simulation accuracy is found among storm events and within the catchment. The simulation results show that the model is able to represent reasonably well the stormflows generated by rainfall events in the study catchment. [ABSTRACT FROM AUTHOR]

Ozone is considered an environmentally friendly alternative for currently applied H[sub 2]SO[sub 4]-based mixtures in the cleaning of semiconductor devices. In order to implement ozone/water cleaning processes in practical systems, fundamental research is needed to understand the underlying chemical processes. Related to the removal of organic contamination from silicon surfaces, one needs to know whether ozone or radical species are the most efficient. A kinetic modeling study is performed to solve this problem whereby the pH is varied and different additives are checked. Theoretical concepts as Dominant Oxidation Pathway (DOP) and Radical Pool (RP) will be introduced for the evaluation of the various reaction pathways. Key Words Ozone; Organics, Semiconductors; Advanced Oxidation Processes; Radicals; Dominant Oxidant Pathway; Radical Pool [ABSTRACT FROM AUTHOR]

Abstract: Landslide problems are abundant in the mountainous areas of Nepal due to a unique combination of adverse geological conditions, abundant rainfall and anthropogenic factors, which leads to enormous loss of life and property every year. To control such problems, systematic studies of landslides are necessary, including inventory mapping and risk assessment. This study applies the analytical hierarchy process method in the Tinau watershed, Nepal. A landslide susceptibility map is prepared on the basis of available digital data of topography, geology, land-use and hydrology. The landslide susceptibility map is validated through physical and statistical methods. The results reveal that the predicted susceptibility levels are found to be in good agreement with the past landslide occurrences, and, hence, the map is trustworthy for future land-use planning. [Copyright &y& Elsevier]

The goal of this paper is to assess the impact of future climate change on the hydrological regime of the tropical Upper Suriname river basin (7,860 km²) located in Suriname. GCM based climate scenarios from the MAGICC/SCENGEN model and 14 hypothetical climate scenarios are used to examine potential changes in water balance components in the study area. A physically-based distributed hydrological model, WetSpa, and Geographic Information Systems (GIS) are used to simulate the historical and future hydrological conditions. The evaluation results indicate that the model has a relatively high confidence (model bias C1 is 0.046 and the model determinant coefficient C2 is 0.833) and can give a fair representation of the river flow hydrographs at daily scale (Nash Sutcliffe coefficient C3 is 0.622). The results indicate that an obvious increase in the annual temperature (1.8°C and 3.2°C by 2050 and 2080 respectively) in the study area is accompanied with a clear tendency in reduced precipitation during January-March and August-December, and an increased tendency during April-July. The sensitivity analyses of water balance components under temperature and precipitation change (GCM scenarios for 2050, 2080) shows that by 2080, the annual river discharge will drop 35%. The hypothetical climate scenarios (T+2°C, T+4°C and P±10%, ±30%, ±50%) however indicate that the annual river discharge will increase with maximum 75% for the scenario T+2°C P+50% and will decrease with maximum 87.5% for the scenario T+2°C P-50%. The results are indications of potential impacts of climate change on water resources in the Upper Suriname river basin, but true predictive skills require a significant improvement in the ability of global climate models to predictive changes in regional climate variability. The WetSpa model has proven to be useful for hydrological modeling studies where availability of physical catchment characteristics and hydroclimatic data is scarce. [ABSTRACT FROM AUTHOR]

This paper presents a Bayesian Monte Carlo method for evaluating the uncertainty in the delineation of well capture zones and its application to a wellfield in a heterogeneous, multiaquifer system. In the method presented, Bayes' rule is used to update prior distributions for the unknown parameters of the stochastic model for the hydraulic conductivity, and to calculate probability-based weights for parameter realizations using head residuals. These weights are then assigned to the corresponding capture zones obtained using forward particle tracking. Statistical analysis of the set of weighted protection zones results in a probability distribution for the capture zones. The suitability of the Bayesian stochastic method for a multilayered system is investigated, using the wellfield Het Rot at Nieuwrode, Belgium, located in a three-layered aquifer system, as an example. The hydraulic conductivity of the production aquifer is modeled as a spatially correlated random function with uncertain parameters. The acquitard and overlying unconfined aquifer are assigned random, homogeneous conductivities. The stochastic results are compared with deterministic capture zones obtained with a calibrated model for the area. The predictions of the stochastic approach are more conservative and indicate that parameter uncertainty should be taken into account in the delineation of well capture zones. [ABSTRACT FROM AUTHOR]

This paper has investigated the importance of explicit instruction and collaborative writing on (a) argumentative writing performance and (b) self-efficacy for writing of secondary school students. This intervention study additionally aimed to evaluate the effectiveness of alternating between individual and collaborative writing throughout the writing process (planning collaboratively, writing individually, revising collaboratively, and rewriting individually). A cluster randomized control trial (CRT) design was opted for. To investigate the effect of the intervention on secondary school students' writing performance and self-efficacy for writing, multilevel analyses were performed. It was found that the presence of explicit instruction in combination with collaborative writing is positively related to argumentative writing performance and self-efficacy for writing. Alternating between individual and collaborative writing was not significantly different from collaborating throughout all phases of the writing process. More in-depth research into the quality of collaboration is, however, needed to gain insight into the interaction processes and writing processes that take place during collaborative writing., Competing Interests: Conflict of InterestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

It is well established that students' motivation for writing is a key predictor of their writing performance. The aim of the current study is to study and map the relations underlying different motivational constructs (i.e., implicit theories, achievement goals, self-efficacy, and writing motives) and to investigate how these contribute to students' writing performance. For that, 390 Flemish students in stage three of the academic track of secondary education (16-18  years old) completed questionnaires measuring their implicit theories of writing, achievement goals, self-efficacy for writing, and writing motives. Furthermore, they completed an argumentative writing test. Path analysis revealed statistically significant direct paths from (1) entity beliefs of writing to performance avoidance goals ( β  = 0.23), (2) mastery goals to self-efficacy for writing ( β argumentation  = 0.14, β regulation  = 0.25, β conventions  = 0.18), performance-approach goals to self-efficacy for writing ( β argumentation  = 0.38, β regulation  = 0.21, β conventions  = 0.25), and performance-avoidance goals to self-efficacy for writing ( β argumentation  = -0.30, β regulation  = -0.24, β conventions  = -0.28), (3) self-efficacy for regulation to both autonomous ( β  = 0.20) and controlled motivation ( β  = -0.15), (4) mastery goals to autonomous motivation ( β  = 0.58), (5) performance approach and avoidance goals to controlled motivation ( β  = 0.18; β  = 0.35), and (6) autonomous motivation to writing performance ( β  = 0.11). This study moves the field of writing motivation research forward by studying the contribution of implicit theories, achievement goals, and self-efficacy to students' writing performance, via writing motives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De Smedt, Landrieu, De Wever and Van Keer.)

Background: Writing is a particularly demanding activity, which poses unique motivational challenges for students. Despite the wealth of research on the relation between writing motivation and writing performance, little is known about the role of students' writing frequency in writing motivation and writing performance., Aims: We aimed to: (1) examine structural relations among two motivational variables (i.e., self-efficacy and attitudes), a behavioural variable (i.e., writing frequency), and writing performance; and (2) inspect whether these relations varied across two text genres (i.e., narrative and opinion texts) and across two educational levels (i.e., students in grades 5-6 and grades 7-8)., Sample: Six hundred and five students from grades 5-8 participated in this study., Methods: Students completed self-report scales and wrote narrative and opinion texts. We conducted multiple-group structural equation modeling to analyse the data., Results: Regarding narrative texts, digital writing frequency was significantly associated with text quality for students in grades 7-8, but this relation was not significant in students from grades 5-6. Both attitudes and self-efficacy for self-regulation made a direct contribution to narrative text quality across educational levels. In addition, attitudes were associated with both literary and digital writing frequency across educational levels. Concerning opinion texts, no significant differences emerged in terms of educational level. Attitudes contributed to both literary and digital writing frequency as well as to opinion text quality across educational levels., Conclusions: This study underlines the fundamental contribution of motivational variables to students' writing performance. Accordingly, teachers need to adopt motivation-enhancing practices in writing instruction across grade levels., (© 2021 The British Psychological Society.)

The twofold aim of this study was to substantiate the validity of the Self-Regulation Questionnaire-Reading Motivation and Self-Regulation Questionnaire-Writing Motivation for third to eight graders and to map motivational trends in elementary and secondary education students' academic and recreational reading and writing. More specifically, we adopted the innovative and coherent theoretical framework of the Self-Determination Theory to study qualitatively different motives for reading and writing and to examine the relationships between them. In total, 2,343 students from third to eighth grade were involved. Based on confirmatory factor analyses, a two-factor model, distinguishing between autonomous and controlled motivation, for academic and recreational reading and writing was confirmed in all grades. Furthermore, the scales were reliable, and the measurement models were invariant across students' gender and their general achievement level. Despite the absence of strong invariance for the measurement models across each of the different grades, we found evidence that students within the same grade level (i.e., middle elementary, upper elementary, and lower secondary grade) interpreted the SRQ-Reading and Writing scale items in a conceptually similar way. Factor correlations confirmed the interrelatedness of reading and writing motives, as well as strong associations between students' motivation to read and write in either academic and recreational contexts. Finally, concerning the motivational trends, the present results advert to a significant decline of students' autonomous motivation to read and write, both in and outside school. Accordingly, we point out that the late elementary and the lower secondary grades are crucial phases to engage students in motivating literacy activities. In light of these alarming results, we recommend future experimental research studies to focus on evaluating the effectiveness of instructional reading and writing activities that foster students' innate need for autonomy, competence, and relatedness., (Copyright © 2020 De Smedt, Rogiers, Heirweg, Merchie and Van Keer.)

Study Question: How does the formation of the blood-testis barrier (BTB), as reflected by the expression of connexin 43 and claudin 11 proteins during the pubertal transition period, take place in vitro compared to samples from a large cohort of pre/peripubertal boys?, Summary Answer: The BTB connexin 43 and claudin 11 expression patterns appeared to be partially achieved in organotypic culture when compared to that in samples from 71 pre/peripubertal patients., What Is Known Already: Although alterations in the protein expression patterns of the BTB, whose main components are connexin 43 and claudin 11, are known to be associated with impaired spermatogenesis in mice and adult men, there is a lack of knowledge on its formation in pre-peripubertal human tissue both in vitro and in vivo. Moreover, despite Sertoli cell (SC) maturation during long-term organotypic culture of immature testicular tissue (ITT), initiation of spermatogenesis has not yet been achieved., Study Design, Size, Duration: Histological sections from 71 pre-peripubertal patients were evaluated for the formation of the BTB acting as in vivo controls according to age, SC maturation, clinical signs of puberty and germ cell differentiation. Testicular tissue fragments retrieved from three prepubertal boys were cultured in a long-term organotypic system to analyze the BTB formation and expression pattern in correlation with SC maturation., Participants/materials, Setting, Methods: Testicular histological sections from 71 patients aged 0-16 years who underwent a biopsy between 2005 and 2014 to preserve their fertility before gonadotoxic treatment were examined. Immunohistochemistry (IHC) results for connexin 43 and claudin 11 as BTB markers, using a semi-quantitative score for their expression, and for Anti-Mullerian hormone (AMH), as SC maturation marker, were analyzed. Germ cell differentiation was evaluated on Hematoxylin-Eosin sections. Tanner stages at the time of biopsy were recorded from medical files. A longitudinal analysis of connexin 43, claudin 11 and AMH expressions on immunohistological sections of organotypic cultured testicular tissue from three prepubertal boys who underwent a biopsy for fertility preservation was performed. Immunostaining was evaluated at culture Days 0, 1, 3, 10, 16, 27, 32, 53, 64 and 139 for two different types of culture media., Main Results and the Role of Chance: Immunohistochemical control sections showed progressive maturation of SCs, as shown by the decrease in AMH expression, with increasing age (P ≤ 0.01) and the AMH expression was negatively correlated with the expression of connexin 43 and claudin 11 (P ≤ 0.01 for both proteins). Androgen receptor (AR) expression increased with age (P ≤ 0.01) and was significantly correlated with the expression of connexin 43 (P = 0.002) and claudin 11 (P = 0.03). A statistical correlation was also found between the reduction of AMH expression and both the advancement of Tanner stages (P ≤ 0.01) and the differentiation of germ cells (P ≤ 0.01). Furthermore, positive correlations between BTB formation (using connexin 43 and claudin 11 expression) and age (P ≤ 0.01 for both the proteins), higher Tanner stages (P ≤ 0.001 and P ≤ 0.01 for connexin 43 and claudin 11, respectively), and presence of more advanced germ cells (P ≤ 0.001 for both proteins) were observed. In the subanalysis on organotypic cultured ITT, where a significant decrease in AMH expression as a marker of SC maturation was already reported, we showed the onset of expression of connexin 43 at Day 16 (P ≤ 0.001) and a constant expression of claudin 11 from Days 0 to 139, for all three patients, without differences between the two types of culture media., Large Scale Data: N/A., Limitations Reasons for Caution: Accessibility of prepubertal human testicular tissue is a major limiting factor to the analysis of cultured tissue samples from a wide number of patients, as would be needed to assess the in vitro development of the BTB according to the age. The impossibility of performing longitudinal studies on in vivo BTB formation in the same patient prevents a comparison of the time needed to achieve effective BTB formation and protein expression patterns in vivo and in vitro., Wider Implications of the Findings: To the best of our knowledge, this is the first report describing the expression of two BTB proteins in samples from a cohort of prepubertal and peripubertal boys, for the in vivo pattern, and in cultured ITT from a few prepubertal boys, for the in vitro evaluation. Since the formation of this barrier is essential for spermatogenesis and because little is known about its protein expression patterns and development in humans, a deeper understanding of the testicular microenvironment is essential to improve ITT in vitro culture conditions. The final aim is to restore fertility by acheiving in vitro differentiation of spermatogonial stem cells, using cryopreserved ITT collected before gonadotoxic therapies., Study Funding and Competing Interest(s): Funding was received from Fonds National de la Recherche Scientifique de Belgique (Grant Télevie Nos. 7.4554.14F and 7.6511.16) and Fondation Salus Sanguinis. No conflict of interest has to be disclosed.

Purpose: To evaluate the precision of hypofractionated radiosurgery using the Gamma Knife Extend relocatable system in patients with benign neoplasms located close to the optic pathways., Methods and Materials: A series of 59 irradiation procedures with the Extend system were performed on 12 patients. We treated 11 meningiomas and 1 craniopharyngioma. All patients except 1 were treated with 5 daily fractions of a 5-Gy margin dose; 1 patient was treated with 4 fractions of 6 Gy. The deviations on the X, Y, and Z axes were calculated as the mean value of all measures performed on each plate of the reposition check tool. An estimation of the patient's head motion during treatment was calculated as the difference between the radial deviations measured before and after each irradiation procedure., Results: The maximum deviation of all measures was 0.9 mm for the 59 procedures. The mean deviations in the X, Y, and Z axes were 0.23 mm (standard deviation [SD], 0.17; maximum, 0.85), 0.31 mm (SD, 0.21; maximum, 0.90), and 0.27 mm (SD, 0.20; maximum, 0.80), respectively. The mean radial intrafraction difference was 0.16 mm (SD 0.14) and the maximum intrafraction deviation was of 0.7 mm. The mean follow-up duration was 19.3 months (range, 6-32 months). The visual status remained stable for 11 patients and improved in 1 patient; the tumor volume remained stable for 4 patients and decreased for 8 patients. From a clinical point of view, no new symptoms were recorded and no vision deterioration occurred., Conclusions: The Extend system provides good repositioning accuracy and adequate immobilization of the patient's head for multisession treatment. The clinical and radiological outcomes of a series of 12 patients who underwent 59 irradiation fractions were excellent., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The objective of the study was to assess the long-term radiological outcome of benign intracranial tumors (BIT) after Gamma Knife radiosurgery. We report the radiological outcome of 280 patients who underwent radiosurgical irradiation for BIT in a single center. Our series included 120 meningiomas, 139 vestibular schwannomas, 12 other schwannomas and 9 pituitary adenomas. Serial imaging studies were performed after irradiation for at least 5 years for all patients. The median tumor volume was 1.9 cc, and the median margin dose was 12 Gy. After a median follow-up of 6.8 years, the tumor control rate was 92.1%: tumor decreased in 176 cases (62.9%), remained unchanged in 82 lesions (29.3%) and increased in 22 cases (7.9%). The actuarial tumor control rate was 93.2% at 5 years, 92.3% at 7.5 years and 91.0% at 10 years. No atypical or malignant transformation of irradiated tumors occured during the follow-up period. Gamma Knife radiosurgery provides a high rate of tumor control for BIT even in the medium to long-term.

Objectives: We analyzed the effects of stereotactic radiosurgery on tumour control and cranial nerve function in patients with vestibular schwannomas (VS) secondary to neurofibromatosis type 2 (NF2). Irradiation was performed with a Gamma Knife, model C equipped with a high-precision, robotized positioning system (APS)., Methodology: This study included 18 patients with 25 VSs secondary to NF2 that were treated from 2001 to 2010 with radiosurgery at our Gamma Knife Center. The radiosurgical procedure included high-resolution conformational dose-planning with multiple, small-diameter isocenters, a single-fraction, low-dose irradiation prescription, and highly accurate gamma rays delivery to the target with the APS., Results: The median follow-up time was 4.4 y. For 16 tumours in 12 patients with available follow-up data, we observed an actuarial tumour control of 87.5% at 2 y and 80.2% at 5 y, based on the Kaplan-Meier method. No patient developed facial weakness. Serviceable hearing was preserved in 78% of cases. Patients treated for bilateral and unilateral tumours had similar outcomes., Conclusions: Radiosurgery could control tumour growth and preserve hearing function and facial weakness in patients with VS secondary to NF2. The enhanced techniques of radiosurgical irradiation provided with the Gamma Knife model C have improved the results of this treatment alternative to microsurgery.

Objective: Concentrations in saliva, as an alternative to concentrations in blood, can be advantageous for the monitoring of antiepileptic agents. This study assesses the relationship between saliva and plasma concentrations of levetiracetam after administration orally as a solution and as a tablet. The possibility that saliva concentrations of the drug are altered by contamination in the buccal cavity was also examined., Methods: 4 healthy male subjects received a single 750 mg oral dose of levetiracetam as a 10% solution and 4 subjects received three 250 mg tablets (750 mg). Levetiracetam concentrations in plasma and saliva were monitored for 24 hours post dose., Results: In subjects receiving the levetiracetam solution, maximum saliva concentrations were observed at the first collection point (15 min) after administration and these were 19-74 times higher than corresponding plasma levels. The mean saliva/plasma ratio rapidly decreased thereafter, becoming stable after 4 hours. In subjects receiving tablets, levetiracetam concentration profiles for saliva paralleled the plasma concentration profiles with a fairly constant saliva/plasma concentration ratio throughout the 24-hour sampling period. A significant linear correlation between levetiracetam saliva and plasma concentrations was demonstrated (Pearson r = 0.88; p < 0.001 for tablet (n = 35) and r = 0.87; p < 0.001 for solution at times > or = 4 hours post-dose (n = 20)). The saliva to plasma concentration ratio was 1.11 (95% confidence interval: 0.99 - 1.22) following tablet intake, and 1.55 (95% CI: 1.34 1.77) following oral solution (> or = 4 hours post dose)., Conclusions: Using saliva to monitor therapeutic exposure to levetiracetam is feasible beginning 15 minutes after tablet intake but beginning 4 hours after intake of an oral solution.

Background: Antiepileptic drugs are usually administere dorally, but alternative routes of drug delivery may be required when oral administration is not feasible., Objective: The purpose of this study was to evaluate the single-dose bioavailability of an IV formulation of levetiracetam relative to oral tablets and the multiple-dose tolerability and pharmacokinetics of this formulation compared with placebo in healthy subjects., Methods: This study consisted of 2 phases. Subjects entered the first phase, which was a single-dose, randomized, open-label, 2-way crossover bioavailability comparison of a 15-minute IV infusion of levetiracetam 1,500 mg and three 500-mg oral tablets. Subjects then entered the second phase, a multiple-dose, randomized, double-blind, placebo-controlled (2:1), parallel-group tolerability and pharmacokinetic study, in which they received 9 successive doses of levetiracetam 1,500 mg IV or placebo at 12-hour intervals. Plasma levetiracetam concentrations were determined by gas chromatography with nitrogen-phosphorus detection. The comparison of bioavailability was based on the 90% CIs around the geometric mean ratios for AUC and C(max) (IV/oral)., Results: Eighteen subjects (9 men, 9 women) participated in the study. All subjects were white. Their mean (SD) age was 35.0 (9.3) years, mean weight 73.3 (14.2) kg, and mean body mass index 23.9 (2.5) kg/m(2). After a single dose, the IV infusion and oral tablet were similar in terms of C(max) (50.5 and 47.7 microg/mL, respectively) and AUC (392.4 and 427.9 pg x h/mL). The geometric mean IV/oral ratios were 92.2 (90 % CI, 89.0-95.6) for AUC and 103.7 (90% CI, 91.6-117.4) for C(max) indicating that the IV and oral formulations were bioequivalent. After multiple twice-daily infusions, steady state was reached within 48 hours. Seventeen (94%) of 18 subjects had >or=1 treatment-emergent adverse event after single-dose administration. During the single-dose phase, the incidence of treatment-emergent adverse events was 89% (16/18) for the IV formulation and 72% (13/18) for the oral tablets; during the multiple-dose phase, the incidence of treatment-emergent adverse events was 67% (8/12) in the IV levetiracetam group and 33% (2/6) in the placebo group. The most common adverse events in the single-dose phase were somnolence (61% IV vs 28% oral) and postural dizziness (17% vs 39%, respectively). The most common adverse events with IV levetiracetam in the multiple-dose phase were also somnolence (33% vs 17% placebo) and postural dizziness (25% vs 0% placebo)., Conclusions: In these healthy subjects, single doses of levetiracetam 1,500 mg administered as a 15-minute IV infusion and as oral tablets were bioequivalent. General and local tolerability during multiple dosing were good. Steady state was reached within 48 hours. Despite the limitations of a study of short duration and small size conducted in healthy subjects, the findings suggest that use of a 15-minute IV infusion of levetiracetam should be further investigated.

The prediction of the location of ground water discharge areas is a key aspect for the protection and (re)development of ground water-dependent wetlands. Ground water discharge areas can be simulated with MODFLOW using the DRAIN package by setting the drain level equal to the topography, while the conductance is mostly set to an arbitrary high value. However, conceptual and practical problems arise in the calculation of the ground water discharge by the DRAIN package as calculated water tables above the land surface, difficult parameterization of the conductance, and large water balance errors. To overcome these problems, a new SEEPAGE package for MODFLOW is proposed. The basic idea of this package is an adaptable constant head cell. It has a variable head, unless the ground water rises above the seepage level, in which case it has a constant head cell. The estimation of the ground water discharge location along a homogeneous, isotropic, linear sloping profile is used to verify the model and to compare it to the DRAIN solution. In an application to three basins in Belgium, it is shown that the SEEPAGE package can be used in combination with the DRAIN package in situations where an upper boundary for a free water table and additional resistance for drainage is required. It is clearly demonstrated that the identification and delineation of regional ground water discharge areas is more accurate using the SEEPAGE package.