Genetic divergence and one-way gene flow influence contemporary evolution and ecology of a partially migratory fish.

Recent work has revealed the importance of contemporary evolution in shaping ecological outcomes. In particular, rapid evolutionary divergence between populations has been shown to impact the ecology of populations, communities, and ecosystems. While studies have focused largely on the role of adaptive divergence in generating ecologically important variation among populations, much less is known about the role of gene flow in shaping ecological outcomes. After divergence, populations may continue to interact through gene flow, which may influence evolutionary and ecological processes. Here, we investigate the role of gene flow in shaping the contemporary evolution and ecology of recently diverged populations of anadromous steelhead and resident rainbow trout (Oncorhynchus mykiss). Results show that resident rainbow trout introduced above waterfalls have diverged evolutionarily from downstream anadromous steelhead, which were the source of introductions. However, the movement of fish from above to below the waterfalls has facilitated gene flow, which has reshaped genetic and phenotypic variation in the anadromous source population. In particular, gene flow has led to an increased frequency of residency, which in turn has altered population density, size structure, and sex ratio. This result establishes gene flow as a contemporary evolutionary process that can have important ecological outcomes. From a management perspective, anadromous steelhead are generally regarded as a higher conservation priority than resident rainbow trout, even when found within the same watershed. Our results show that anadromous and resident O. mykiss populations may be connected via gene flow, with important ecological consequences. Such eco-evolutionary processes should be considered when managing recently diverged populations connected by gene flow.

The consensus of the Asociación Mexicana de Gastroenterología on the diagnosis and treatment of gastroesophageal reflux and gastroesophageal reflux disease in infants.

Gastroesophageal reflux (GER) is a frequent normal phenomenon in children of any age. It is more common in infants, in whom the majority of episodes are short-lived and cause no other symptoms or complications, differentiating it from gastroesophageal reflux disease (GERD). The diagnosis and management of GER and GERD continue to be a challenge for the physician. Therefore, the aim of the Asociación Mexicana de Gastroenterología was to adapt international documents to facilitate their adoption by primary care physicians, with the goal of standardizing quality of care and reducing the number of diagnostic tests performed and inappropriate medication use. The ADAPTE methodology was followed, and the recommendations were approved utilizing the Delphi strategy. The executive committee carried out the review of the guidelines, position papers, and international reviews that met the a priori quality criteria and possible applicability in a local context. The recommendations were taken from those sources and adapted, after which they were approved by the working group. The consensus consists of 25 statements and their supporting information on the diagnosis and treatment of GER and GERD in infants. The adapted document is the first systematic effort to provide an adequate consensus for use in Mexico, proposing a practical approach to and management of GER and GERD for healthcare providers.

Definition and Diagnostic Criteria for Pediatric Blepharokeratoconjunctivitis.

Importance: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. Objective: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. Design, Setting, and Participants: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. Results: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was "pediatric blepharokeratoconjunctivitis," and the agreed-on definition was "Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring." The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. Conclusions and Relevance: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel's clinical experience, requiring further validation with real patient data analysis.

Screws versus plate with screws for osteosynthesis of the posterior malleolus: a systematic review and meta-analysis.

INTRODUCTION: fractures involving the posterior malleolus (PM) of the ankle can have significant functional and clinical implications if not properly treated. The optimal treatment approach for these fractures remains uncertain. This review aims to compare the use of cannulated screws versus plate with screw fixation in terms of their impact on the development of postoperative ankle osteoarthritis and functional outcomes in patients with PM fractures. MATERIAL AND METHODS: a comprehensive search was conducted in PubMed, EMBASE, and Cochrane Library databases to identify studies directly comparing cannulated screws versus plate with screw fixation for PM fractures and their association with the development of postoperative osteoarthritis and functional outcomes. The quality of the included studies was assessed using appropriate assessment tools. The data on osteoarthritis development and functional outcomes were extracted and analyzed. RESULTS: a total of 691 articles were screened, and several studies were included for analysis. The findings revealed no statistically significant difference in the development of postoperative ankle osteoarthritis between the cannulated screws and plate with screw fixation groups. Similarly, there was no significant difference in functional outcomes between the two treatment approaches. CONCLUSION: based on the available evidence, there is no significant difference in the development of postoperative ankle osteoarthritis or functional outcomes between cannulated screws and plate with screw fixation for PM fractures. However, further research is needed to strengthen these findings and provide more conclusive evidence.

INTRODUCCIÓN: las fracturas que involucran el maléolo posterior (MP) del tobillo pueden tener importantes implicaciones funcionales y clínicas si no se tratan adecuadamente. El enfoque de tratamiento óptimo para estas fracturas sigue siendo incierto. El objetivo de esta revisión es comparar el uso de tornillos canulados versus placa con fijación de tornillos en cuanto a su impacto en el desarrollo de la osteoartrosis de tobillo postoperatoria y los resultados funcionales en pacientes con fracturas del MP. MATERIAL Y MÉTODOS: se realizó una búsqueda exhaustiva en las bases de datos de PubMed, EMBASE y Cochrane Library para identificar estudios que compararan directamente tornillos canulados versus placa con fijación de tornillos para fracturas de MP y su asociación con el desarrollo de osteoartrosis postoperatoria y los resultados funcionales. La calidad de los estudios incluidos se evaluó utilizando herramientas de evaluación adecuadas. Los datos sobre el desarrollo de osteoartrosis y los resultados funcionales se extrajeron y analizaron. RESULTADOS: se revisaron un total de 691 artículos y se incluyeron varios estudios para su análisis. Los hallazgos revelaron que no hay una diferencia estadísticamente significativa en el desarrollo de osteoartrosis de tobillo postoperatoria entre los grupos de tornillos canulados y placa con fijación de tornillos. Del mismo modo, no hubo una diferencia significativa en los resultados funcionales entre los dos enfoques de tratamiento. CONCLUSIÓN: según la evidencia disponible, no hay una diferencia significativa en el desarrollo de osteoartrosis de tobillo postoperatoria o en los resultados funcionales entre los tornillos canulados y la placa con fijación de tornillos para las fracturas del MP. Sin embargo, se necesita más investigación para fortalecer estos hallazgos y proporcionar evidencia más concluyente.

Proposed anti-seizure medication combinations with rufinamide in the treatment of Lennox-Gastaut syndrome: Narrative review and expert opinion.

Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5 Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such "rational polytherapy" involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors' clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS.

Screws versus plate with screws for osteosynthesis of the posterior malleolus: a systematic review and meta-analysis / Tornillos frente a placa con tornillos para la osteosíntesis del maléolo posterior: una revisión sistemática y meta-análisis

Abstract: Introduction: fractures involving the posterior malleolus (PM) of the ankle can have significant functional and clinical implications if not properly treated. The optimal treatment approach for these fractures remains uncertain. This review aims to compare the use of cannulated screws versus plate with screw fixation in terms of their impact on the development of postoperative ankle osteoarthritis and functional outcomes in patients with PM fractures. Material and methods: a comprehensive search was conducted in PubMed, EMBASE, and Cochrane Library databases to identify studies directly comparing cannulated screws versus plate with screw fixation for PM fractures and their association with the development of postoperative osteoarthritis and functional outcomes. The quality of the included studies was assessed using appropriate assessment tools. The data on osteoarthritis development and functional outcomes were extracted and analyzed. Results: a total of 691 articles were screened, and several studies were included for analysis. The findings revealed no statistically significant difference in the development of postoperative ankle osteoarthritis between the cannulated screws and plate with screw fixation groups. Similarly, there was no significant difference in functional outcomes between the two treatment approaches. Conclusion: based on the available evidence, there is no significant difference in the development of postoperative ankle osteoarthritis or functional outcomes between cannulated screws and plate with screw fixation for PM fractures. However, further research is needed to strengthen these findings and provide more conclusive evidence.

Resumen. Introducción: las fracturas que involucran el maléolo posterior (MP) del tobillo pueden tener importantes implicaciones funcionales y clínicas si no se tratan adecuadamente. El enfoque de tratamiento óptimo para estas fracturas sigue siendo incierto. El objetivo de esta revisión es comparar el uso de tornillos canulados versus placa con fijación de tornillos en cuanto a su impacto en el desarrollo de la osteoartrosis de tobillo postoperatoria y los resultados funcionales en pacientes con fracturas del MP. Material y métodos: se realizó una búsqueda exhaustiva en las bases de datos de PubMed, EMBASE y Cochrane Library para identificar estudios que compararan directamente tornillos canulados versus placa con fijación de tornillos para fracturas de MP y su asociación con el desarrollo de osteoartrosis postoperatoria y los resultados funcionales. La calidad de los estudios incluidos se evaluó utilizando herramientas de evaluación adecuadas. Los datos sobre el desarrollo de osteoartrosis y los resultados funcionales se extrajeron y analizaron. Resultados: se revisaron un total de 691 artículos y se incluyeron varios estudios para su análisis. Los hallazgos revelaron que no hay una diferencia estadísticamente significativa en el desarrollo de osteoartrosis de tobillo postoperatoria entre los grupos de tornillos canulados y placa con fijación de tornillos. Del mismo modo, no hubo una diferencia significativa en los resultados funcionales entre los dos enfoques de tratamiento. Conclusión: según la evidencia disponible, no hay una diferencia significativa en el desarrollo de osteoartrosis de tobillo postoperatoria o en los resultados funcionales entre los tornillos canulados y la placa con fijación de tornillos para las fracturas del MP. Sin embargo, se necesita más investigación para fortalecer estos hallazgos y proporcionar evidencia más concluyente.

Postreperfusion Syndrome in Liver Transplant: A Risk Factor for Acute Kidney Failure: A Retrospective Analysis.

The maximum expression of hemodynamic instability during liver transplant is the so-called postreperfusion syndrome (PRS) that increases both overall mortality and postoperative complications. It was first defined by Aggarwal et al in 1987, but the results are still conflicting when establishing the relationship between PRS and acute kidney failure (AKF). We conducted a retrospective observational study of transplant recipients with deceased-donor liver grafts between January 2002 and December 2018. We analyzed the incidence of PRS and its potential negative impact over kidney function. A total of 551 transplants were analyzed. PRS was recorded in 130 patients (23.6%). The incidence of AKF was 61.5%. A total of 111 patients required kidney replacement therapy (32.7%). Regarding the severity of AKF, 128 patients were classified as acute kidney injury (AKI) 1 (23.2%), 76 as AKI 2 (13.8%), and 135 as AKI 3 (24.5%). In the group with PRS, 75.4% (n = 98) developed AKF vs 57.2% (n = 241) in the group without PRS. In the multivariate analysis we found a relationship between PRS and AKF with an odds ratio of 2.18 (95% CI, 1.30-3.64; P = .003), once adjusted by the length of the anhepatic phase, donor age, Model for End-Stage Liver Disease score, history of ascites, and need for early surgical reintervention. The incidence of AKF decreased (44.5%) ever since the implementation of delayed calcineurin inhibitors therapy and piggyback surgical technique, but a clear influence of the occurrence of PRS on the development of AKF is still observed, with an OR of 3.78 (95% CI, 1.92-7.43; P < .001), once adjusted by albumin and hemoglobin levels, Model for End-Stage Liver Disease score, and Child classification.

Assessment of the long-term efficacy and safety of adjunctive perampanel in adolescent patients with epilepsy: Post hoc analysis of open-label extension studies.

OBJECTIVE: This post hoc analysis of four open-label extension (OLEx) studies evaluated the long-term efficacy and safety of adjunctive perampanel in adolescent patients (aged 12 to ≤17 years) with focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS). METHODS: Patients who completed one of six double-blind, placebo-controlled studies could enter one of four OLEx studies comprising a blinded Conversion Period (6-16 weeks) followed by a Maintenance Phase (27 to ≤256 weeks; perampanel dose: ≤12 mg/day). Exposure, retention, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. Efficacy outcomes were analyzed using observed case and last observation carried forward (LOCF) approaches; the latter was used to account for early dropouts. RESULTS: The Full Analysis Set comprised 309 adolescents with FOS (FBTCS, n = 109) and 19 with GTCS, and the Safety Analysis Set comprised 311 with FOS (FBTCS, n = 110) and 19 with GTCS. Mean (standard deviation) cumulative duration of perampanel exposure (weeks) was: FOS, 77.7 (58.7); FBTCS, 88.7 (63.8); and GTCS, 97.0 (35.5). Retention rates were maintained for ≤2 years (FOS, 50.0 %; FBTCS, 57.1 %; GTCS, 41.7 %). Seizure control (median percent reduction in seizure frequency/28 days) was sustained for up to 2 years; FOS (59.4 %, n = 113), FBTCS (64.6 %, n = 53), and GTCS (86.5 %, n = 17). At Year 2, 50 % responder rates were: FOS, 58.4 % (n = 66); FBTCS, 54.7 % (n = 29); and GTCS, 82.4 % (n = 14); seizure-freedom rates were: FOS, 5.3 % (n = 6); FBTCS, 24.5 % (n = 13); and GTCS, 35.3 % (n = 6). Long-term seizure control was observed even in LOCF analyses. The incidence of TEAEs was highest during Year 1 (FOS, n = 269 [86.5 %]; FBTCS, n = 95 [86.4 %]; GTCS, n = 15 [78.9 %]), compared with Years 2-4; the most common (≥10 % of patients) were dizziness, somnolence, and nasopharyngitis. No new safety signals emerged with long-term treatment. CONCLUSIONS: This post hoc analysis suggests that long-term (≤2 years) adjunctive perampanel (≤12 mg/day) is efficacious and generally well tolerated in adolescent patients with FOS, with or without FBTCS, or GTCS.

Volumetric assessment of the sella turcica: a re-evaluation.

BACKGROUND: The sella turcica volume is widely measured by the Di Chiro-Nelson method. The purpose is to compare the fidelity of a proposed volumetry method vs. the Di Chiro-Nelson method, using computed tomography (CT) images. MATERIALS AND METHODS: Morphometric examination of 173 CT scans were included, of which 52.6% were female. The mean age was 53.2 ± 17.6 years. Considering the Di Chiro-Nelson method, two measurements were added for each axis in the CT evaluation: length (central, left, and right), width (central, anterior, and posterior), and height (central, left, and right). RESULTS: The mean measurements were length: central 10.11 ± 1.44, left 7.45 ± 1.67, right 7.53 ± 1.59; width: central 12.27 ± 2.11, anterior 10.99 ± 1.92, posterior 10.10 ± 1.74; height: central 7.68 ± 1.38, left 7.16 ± 1.35, right 7.40 ± 1.41. A statistically significant difference between sexes was found only in the anterior width (p = 0.01). Using the proposed method, the volume was 342.2 ± 88.5 and 378. 6 ± 113.9 mm³, respectively for females and males (p = 0.02) vs. 476.1 ± 132.4 and 523.8 ± 186.0 mm3 (p = 0.05) using the Di Chiro-Nelson's method. CONCLUSIONS: Women had significantly smaller sella turcica volume than men. This proposed method considers the sella turcica as a not strictly symmetrical structure and indicates reduced variation between the maximum and minimum values, compared to the Di Chiro-Nelson's. Our findings may be useful for reassessment the volume of the sella turcica as the measurements indicate a higher precision.

Nanocomposite PLA/C20A Nanoclay by Ultrasound-Assisted Melt Extrusion for Adsorption of Uremic Toxins and Methylene Blue Dye.

Design of functional materials it is of great importance to address important problems in the areas of health and environment. In the present work, the synthesis and application of poly-meric nanocomposite materials with poly (lactic acid) (PLA) and modified nanoclay (cloisite 20A) with 1,4-diaminobutane dihydrochloride at different reaction times were studied. The concentra-tions of the nanoclays in the PLA matrix were 0.5, 1 and, 5% by weight (wt%). TGA showed that sample C20AM 120 (120 min of treatment) obtained the highest degree of modification considering the weight losses of the analyzed samples. An FT-IR signal at 1443 cm-1 suggests that the organic modifier is intercalated between the galleries of the clay. XRD, SEM and XPS suggest good disper-sion at low concentrations of the nanoclay. Adsorption tests revealed that the highest percentage of removal of uremic toxins and methylene blue was the sample with 5% wt/wt chemically modified nanoclay, suggesting good affinity between the modified nanoclays in the PLA matrix with the nitrogenous compounds.

Severe bowel complications in SARS-CoV-2 patients receiving protocolized care.

INTRODUCTION AND AIMS: A case series of ten patients that received protocolized care for SARS-CoV-2 infection and developed severe gastrointestinal complications, is presented. The aim of our study was to contribute to the ongoing discussion regarding gastrointestinal complications related to SARS-CoV-2 infection. After reviewing the current literature, ours appears to be the first detailed case series on the topic. MATERIALS AND METHODS: A retrospective filtered search of all patients admitted to our hospital for SARS-CoV-2 infection, who developed severe gastrointestinal complications, was performed. All relevant data on hospital patient management, before and after surgery, were collected from the medical records. RESULTS: Of the 905 patients admitted to our hospital due to SARS-CoV-2 infection, as of August 26, 2020, ten of them developed severe gastrointestinal complications. Seven of those patients were men. There were four cases of perforation of the proximal jejunum, three cases of perforations of the ascending colon, one case of concomitant perforation of the sigmoid colon and terminal ileum, one case of massive intestinal necrosis, and one preoperative death. Three right colectomies, four intestinal resections, one Hartmann's procedure with bowel resection, and one primary repair of the small bowel were performed. The mortality rate of the patients analyzed was 50%. CONCLUSION: Spontaneous bowel perforations and acute mesenteric ischemia are emerging as severe, life-threatening complications in hospitalized SARS-CoV-2 patients. More evidence is needed to identify risk factors, establish preventive measures, and analyze possible adverse effects of the current treatment protocols.

Abnormal liver function tests in acne patients receiving isotretinoin.

BACKGROUND: Isotretinoin is an efficacious treatment option for severe acne. Although isotretinoin often causes mild liver enzyme elevation, how acne patients should be monitored on isotretinoin therapy is not well characterized. OBJECTIVE: The purpose of this study was to assess the management and clinical outcome of acne patients with abnormal aspartate transaminase (AST) and alanine aminotransferase (ALT) when receiving isotretinoin. METHODS: A retrospective chart review was conducted in acne subjects with abnormal AST and ALT levels receiving isotretinoin. Abnormal liver enzymes were graded using the Common Terminology Criteria for Adverse Events version 5. RESULTS: Of 108 subjects with abnormal liver enzymes, 79 subjects were on isotretinoin 80 mg and 23 subjects were on isotretinoin 40 mg. Most abnormalities were during Month 1 of therapy (48). Of the 122 abnormal Grade 1 AST elevations, 40 normalized, 38 remained in Grade 1, and 1 increased into Grade 2 when a healthcare provider maintained the isotretinoin dose. Of the 102 abnormal Grade 1 ALT levels managed by maintaining the isotretinoin dose, 31 normalized and 38 remained persistently elevated. CONCLUSION: Most mild elevations of isotretinoin therapy do not worsen. Acne patients with isotretinoin may not need continued testing when experiencing low-grade liver enzyme abnormalities.

[Severe bowel complications in SARS-CoV-2 patients receiving protocolized care]. / Complicaciones intestinales graves en pacientes SARS-CoV-2 recibiendo manejo protocolizado.

Introduction and aims: A case series of ten patients that received protocolized care for SARS-CoV-2 infection and developed severe gastrointestinal complications, is presented. The aim of our study was to contribute to the ongoing discussion regarding gastrointestinal complications related to SARS-CoV-2 infection. After reviewing the current literature, ours appears to be the first detailed case series on the topic. Materials and methods: A retrospective filtered search of all patients admitted to our hospital for SARS-CoV-2 infection, who developed severe gastrointestinal complications, was performed. All relevant data on hospital patient management, before and after surgery, were collected from the medical records. Results: Of the 905 patients admitted to our hospital due to SARS-CoV-2 infection, as of August 26, 2020, ten of them developed severe gastrointestinal complications. Seven of those patients were men. There were four cases of perforation of the proximal jejunum, three cases of perforations of the ascending colon, one case of concomitant perforation of the sigmoid colon and terminal ileum, one case of massive intestinal necrosis, and one preoperative death. Three right colectomies, four intestinal resections, one Hartmann's procedure with bowel resection, and one primary repair of the small bowel were performed. The mortality rate of the patients analyzed was 50%. Conclusion: Spontaneous bowel perforations and acute mesenteric ischemia are emerging as severe, life-threatening complications in hospitalized SARS-CoV-2 patients. More evidence is needed to identify risk factors, establish preventive measures, and analyze possible adverse effects of the current treatment protocols.

Long-term safety and tolerability of adjunctive eslicarbazepine acetate in children with focal seizures.

OBJECTIVE: The objective of this study was to evaluate long-term safety and tolerability outcomes in two open-label extension (OLE) studies of adjunctive eslicarbazepine acetate (ESL) in children with focal seizures. METHODS: Safety data from patients aged 4-17 years in OLEs of Studies 2093-208 and -305 were pooled and analyzed. Studies 208 and 305 were randomized, double-blind, placebo-controlled studies of adjunctive treatment with ESL in children with focal seizures refractory to treatment with 1-2 antiseizure drugs; patients could continue into uncontrolled OLEs (up to 5 years total duration). The OLEs evaluated the safety and tolerability of ESL (10-30 mg/kg/day; maximum 1200 mg/day). RESULTS: The 1-year OLE and post-1-year OLE safety populations comprised 337 and 177 ESL-treated patients, respectively. The overall incidence of treatment-emergent adverse events (TEAEs) with ESL was 64.1% during the 1-year OLE and 52.5% during the post-1-year OLE. Nasopharyngitis, partial seizures, vomiting, pyrexia, headache, somnolence, and respiratory tract infection were the most frequently reported TEAEs during the 1-year OLE. The overall incidence of serious adverse events (AEs) was 8.9% during the 1-year OLE and 10.2% during the post-1-year OLE. Partial seizures (1.2%) and pneumonia (1.2%) were the most frequently reported serious AEs during the 1-year OLE. The overall incidence of TEAEs leading to discontinuation was 4.2% during the 1-year OLE and 0.6% during the post-1-year OLE. Partial seizures (1.5%) was the most frequently reported TEAE leading to discontinuation during the 1-year OLE. CONCLUSIONS: Overall, long-term treatment with ESL was generally well tolerated in pediatric patients aged 4-17 years with focal seizures. TEAEs were comparable to those observed in adults with no new events of concern.

NWChem: Past, present, and future.

Specialized computational chemistry packages have permanently reshaped the landscape of chemical and materials science by providing tools to support and guide experimental efforts and for the prediction of atomistic and electronic properties. In this regard, electronic structure packages have played a special role by using first-principle-driven methodologies to model complex chemical and materials processes. Over the past few decades, the rapid development of computing technologies and the tremendous increase in computational power have offered a unique chance to study complex transformations using sophisticated and predictive many-body techniques that describe correlated behavior of electrons in molecular and condensed phase systems at different levels of theory. In enabling these simulations, novel parallel algorithms have been able to take advantage of computational resources to address the polynomial scaling of electronic structure methods. In this paper, we briefly review the NWChem computational chemistry suite, including its history, design principles, parallel tools, current capabilities, outreach, and outlook.