Comparative Outcomes of Minimally Invasive Versus Open Pancreatoduodenectomy in Distal Cholangiocarcinoma: A Systematic Review and Meta-Analysis.

Pancreatoduodenectomy, the primary surgical strategy for managing cholangiocarcinoma, is executed via two distinct methodologies, namely minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD). The selection between these surgical options is critical, as it directly influences patient outcomes, encompassing both short-term recovery metrics and long-term survival rates. Despite the clinical significance of these procedures, there exists a notable void in the literature regarding a comprehensive comparison of MIPD and OPD, particularly in assessing their respective efficacies and complications. This lack of detailed comparative analysis has left a gap in evidence-based guidance for clinicians faced with the decision of choosing the most appropriate surgical approach for their patients. The absence of robust data comparing the two techniques underscores the necessity for a meta-analysis that rigorously examines and contrasts the outcomes associated with MIPD and OPD. By drawing upon a wide array of international studies, this research aims to shed light on the advantages and potential drawbacks of each method, thereby providing a more informed basis for surgical decision-making in the treatment of cholangiocarcinoma.

Elucidating jejunal diverticulosis: Diagnostic and treatment insights from a perforated case study.

INTRODUCTION AND IMPORTANCE: Diverticula are sac-shaped formations resulting from the inward folding of the intestinal wall's lining. While they predominantly occur in the colon, they can manifest in other parts of the gastrointestinal tract, with jejunal diverticulum being the most prevalent. Symptoms are infrequent in most cases, and when they do occur, intestinal perforation is the most severe complication. In such instances, prompt surgical intervention is imperative, typically entailing the excision of the affected intestinal segment, followed by a end-to-end anastomosis. CASE PRESENTATION: A 75-year-old female patient presented at the emergency department with sharp abdominal pain. Imaging revealed the presence of perforated jejunal diverticula. Diagnostic laparoscopy confirmed a perforated jejunal diverticulum along with generalized peritonitis and multiple diverticula in the same region. Consequently, we performed a segmental intestinal resection and anastomosis. CLINICAL DISCUSSION: Jejunal diverticulosis, a rare condition primarily affecting the elderly, is found in 0.5-2.3 % of imaging studies. Although its exact cause remains elusive, potential contributing factors include abnormal intestinal movements and elevated gut pressure. Symptoms are generally vague, such as abdominal discomfort. Diagnosis often occurs incidentally during imaging, leading to a high mortality rate when complications occurs. While computed tomography (CT) scans are useful for detecting intestinal wall protrusions, definitive diagnosis typically requires laparoscopy or laparotomy. Treatment varies based on symptoms and complications, with surgery often necessary for perforations or when medical treatment fails. CONCLUSION: Jejunal diverticulosis is often asymptomatic or displays non-specific symptoms. Timely diagnosis and prompt surgical intervention in case of perforation is crucial.

Transitioning insomnia patients from zolpidem to lemborexant: A multicenter, open-label study evaluating a next-dose transition approach to insomnia pharmacotherapy.

Objective: Few clinical studies have assessed real-world abrupt transitioning between insomnia medications. This study assessed strategies for directly transitioning patients from zolpidem tartrate (ZOL) immediate/extended release to the dual orexin receptor antagonist, lemborexant (LEM). Methods: This randomized, open-label, multicenter study (Study 312; E2006-A001-312) enrolled 53 adults age ≥18 years with insomnia disorder and ≥1-month history of intermittent (3-4 nights/week) or frequent (≥5 nights/week) ZOL use. Subjects recorded their ZOL use in a 3-week Pretreatment Phase, followed by a 2-week Treatment Phase (TRT; Titration) during which ZOL was discontinued. Intermittent ZOL users transitioned to LEM 5 mg (LEM5), Cohort 1, and frequent ZOL users were randomized 1:1 to LEM5, Cohort 2A, or LEM 10 mg (LEM10), Cohort 2B. One dose adjustment was permitted during the TRT. Subjects completing the TRT could continue LEM in the 12-week Extension Phase (EXT). The primary outcome was proportion of subjects who successfully transitioned and remained on LEM at the end of the TRT. Results: Most subjects (43 [81.1 %]) successfully transitioned to LEM (9 [90 %], 17 [81.0 %], and 17 [77.3 %] in Cohorts 1, 2A, and 2B, respectively). By the end of the EXT, 66.7 % in Cohort 1 and 60.0 % in Cohort 2A up-titrated to LEM10, whereas 41.2 % in Cohort 2B down-titrated to LEM5; 61.0 % were receiving LEM10 at study end. At the end of the TRT, more subjects taking LEM reported that it helped them return to sleep after waking, compared with those taking ZOL (71.7 % vs. 49.1 %). There were no important differences between treatments regarding how subjects reported feeling as they fell asleep. Most of the treatment-emergent adverse events with LEM were mild in severity. Conclusions: Most subjects transitioned successfully to LEM from ZOL (intermittent or frequent use). LEM was well tolerated.

Efficacy and safety of lemborexant in subjects previously treated with placebo for 6 months in a randomized phase 3 study.

OBJECTIVE/BACKGROUND: To examine the effects of lemborexant (LEM) 5 mg (LEM5) or LEM 10 mg (LEM10) following extended placebo treatment. This post-hoc analysis used subject-reported sleep outcomes data from a phase 3 trial. PATIENTS/METHODS: The subjects in these post-hoc analyses were randomized to placebo for 6 months (Time Period [TP]1) in Study E2006-G000-303 (SUNRISE-2; NCT02952820). Following placebo exposure, subjects were re-randomized to LEM5 or LEM10 for another 6 months (TP2). Subject-reported sleep outcomes derived from sleep diaries included sleep onset latency (sSOL), wake after sleep onset (sWASO), sleep efficiency (sSE), and total sleep time (sTST). Magnitude and change rate in parameters were assessed for 7 days before/after initial randomization to placebo and 7 days before/after re-randomization to LEM (6 months later). Month 6 placebo non-responders were assessed for LEM response in TP2 using predetermined responder definitions. Safety was monitored throughout the study. RESULTS: Overall, 321 subjects received placebo; 258 re-randomized subjects received LEM5 (n = 133) and LEM10 (n = 125). Subjective sleep outcomes improved during TP1 with approximately 62 subjects (∼20%) exhibiting a sustained placebo response. Upon re-randomization to LEM, all measures showed an additional incremental benefit, most prominently in sSOL and sTST. Among Month 6 placebo non-responders, 11%-15% subsequently responded to LEM as assessed at Month 12. The safety profile was similar between treatment periods and treatment groups. CONCLUSIONS: These data suggest that even when insomnia symptoms have improved over time with placebo treatment, additional and sustained clinical gains in sleep outcomes are possible with active treatment using lemborexant.

Tunable Mid-Infrared Interband Emission from Tensile-Strained InGaAs Quantum Dots.

We demonstrate the ability to tailor self-assembled growth of In0.5Ga0.5As quantum dots (QDs) on GaSb(111)A surfaces by molecular beam epitaxy. Spontaneous formation via the Volmer-Weber growth mode produces QDs with excellent structural and optical quality. By harnessing tensile strain to reduce their band gap energy, these QDs are characterized by light emission that extends into the midwave infrared wavelength range of 3.2-3.9 µm (0.318-0.388 eV). As we increase QD size, we can tune the band alignment from type-III to type-II, where light emission occurs due to interband recombination between quantum confined electrons in the InGaAs QDs and holes in the GaSb barriers. Of particular interest is an unusual blue-shift in emission wavelength with increasing QD size, which we attribute to the incorporation of Sb into the InGaAs QDs from the GaSb barriers. By expanding this approach to produce tensile-strained QDs from other narrow band gap semiconductors, we anticipate the development of a range of highly tunable mid-infrared light sources.

Improvement in fatigue and sleep measures with the dual orexin receptor antagonist lemborexant in adults with insomnia disorder.

OBJECTIVE: Fatigue is a common symptom in patients with insomnia. This analysis evaluated whether treatment of nighttime symptoms of insomnia with a dual orexin receptor antagonist, lemborexant, might also reduce fatigue. METHODS: Analyses were conducted of two phase 3 studies of subjects with insomnia disorder. Subjects received placebo, lemborexant 5 mg, or lemborexant 10 mg in the 12-month (6 months placebo-controlled) Study E2006-G000-303 (Study 303: SUNRISE-2) of adults (N = 949; full analysis set [FAS]), and the 1-month, placebo- and active-controlled Study E2006-G000-304 (Study 304; SUNRISE-1) of older adults (females ≥55 years, males ≥65 years) (N = 1006; FAS). Fatigue was assessed using the Fatigue Severity Scale (FSS). Patient-reported sleep onset and maintenance endpoints were analyzed using data from electronic sleep diaries. RESULTS: Lemborexant significantly reduced subject-reported fatigue versus placebo over a 6-month treatment period (FSS total score least-squares mean treatment difference of -2.50 for 5 mg and -2.56 for 10 mg of lemborexant; p < 0.05 for both). This reduction was sustained over 12 months of lemborexant in both the overall population and in subjects with clinically meaningful fatigue (FSS total score ≥36) at baseline. Improvements in fatigue over time positively correlated with improvements in sleep onset and maintenance parameters. Improvements in sleep quality were evident as early as 1 week after lemborexant treatment, whereas longer-term treatment (>1 month) may be needed for improvements in insomnia-related fatigue. CONCLUSIONS: In addition to improving sleep onset and sleep maintenance in subjects with insomnia disorder, lemborexant provides further benefit by reducing daytime fatigue. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02952820 and https://clinicaltrials.gov/ct2/show/NCT02783729. ABBREVIATIONS: DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; FSS = Fatigue Severity Scale; ICSD-3 = International Classification of Sleep Disorders, Third Edition; LSM = least squares mean; sSE = subjective sleep efficiency; sSOL = subjective sleep onset latency; sTST = subjective total sleep time; sWASO = subjective sleep after wake onset.

Impact of lemborexant treatment on insomnia severity: analyses from a 12-month study of adults with insomnia disorder.

OBJECTIVE/BACKGROUND: Evaluate changes in insomnia severity in subjects with moderate to severe insomnia (Insomnia Severity Index [ISI] score ≥15) treated for 12 months nightly with lemborexant. PATIENTS/METHODS: This phase 3 randomized study comprised two 6-month treatment periods. In Period 1, 949 subjects were randomized to placebo, lemborexant 5 mg (LEM5) or 10 mg (LEM10). In Period 2, placebo subjects were rerandomized to LEM5 or LEM10; subjects initially randomized to lemborexant continued their assigned treatment. Insomnia severity was assessed using baseline ISI and 1-, 3-, 6-, 9-, and 12-month post-treatment scores. RESULTS: Mean ISI scores improved significantly across treatment groups and disease severities, with greater decreases from baseline in the LEM5 and LEM10 versus placebo groups at months 1 (-7.1, -7.2, -5.2, respectively), 3 (-8.6, -8.9, -6.1, respectively), and 6 (-9.9, -9.8, -7.2 respectively); ISI score improvements were maintained with LEM5 and LEM10 at months 9 (-11.1 and -11.2, respectively) and 12 (-11.5 and -11.2, respectively). At months 1, 3, and 6, significantly more treatment responders (≥7-point ISI score decrease from baseline) were observed with LEM5 (44%-57%) and LEM10 (44%-52%) versus placebo (30%-41%). At months 1, 3, and 6, more remitters (ISI total score <10 and < 8) were observed with LEM5 (30%-44% and 22%-34%, respectively) and LEM10 (31%-41% and 22%-31%, respectively) versus placebo (18%-28% and 11%-21%, respectively). CONCLUSIONS: Lemborexant significantly reduced insomnia severity for 12 months and increased clinically meaningful response and remission rates versus placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Cephalexin removal by persulfate activation using simulated sunlight and ferrous ions.

This study presents the main results related to the use of activated persulfate (PS) in the elimination of the beta-lactam antibiotic cephalexin (CPX). Experiments were done using K2S2O8 and simulated sunlight. A face-centered central composite experimental design was used to analyze the effects of the solution pH and the PS concentration on the reaction, and to determine the optimized conditions that favor the CPX elimination. The results indicated that the removal of CPX is promoted by an acidic pH and under the higher evaluated PS dose (7.5 mg L-1). CPX total removal was achieved in 30 min. The analysis of the effect of the pollutant initial concentration indicated that a pseudo-first-order kinetics model can be used to describe the reaction. Likewise, the use of Fe2+ ions for PS activation (in the dark) was evaluated and established that a higher concentration of ions favors the pollutant removal. Control tests and under the presence of scavenger agents indicated that both HO• and SO4-• radicals would be present in the solution and promote the CPX elimination. The assessment of the solution dissolved organic carbon, nitrates and sulfates was also carried out, and indicated that a portion of the organic matter was mineralized.

Safety and efficacy of rufinamide in children and adults with Lennox-Gastaut syndrome: A post hoc analysis from Study 022.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy with the first symptoms usually appearing during early childhood. Due to the highly variable underlying etiologies, LGS cannot be considered as one disease but as an electro-clinical entity, often challenging to diagnose early and treat accordingly. The anti-seizure medication, rufinamide, is indicated for the adjunctive treatment of patients with LGS aged ≥1 year. This post hoc analysis assessed the safety and efficacy of adjunctive rufinamide for total and tonic-atonic seizures during Study 022 in children (aged <16 years) and adults (aged ≥16 years). METHODS: Randomized, placebo-controlled, phase III Study 022 included patients with a diagnosis of LGS and a history of multiple seizure types (including tonic-atonic or astatic seizures and atypical absence seizures; ≥90 seizures in the month prior to baseline). Assessments included monitoring of treatment-emergent adverse events (TEAEs), percent change in tonic-atonic seizure frequency/28 days during the double-blind phase relative to study baseline (a primary endpoint), and percentage of patients with ≥25%, ≥50%, or ≥75% reduction in seizure frequency relative to baseline. RESULTS: Of 138 enrolled patients, 74 received rufinamide (<16 years, n = 49 [66%]) and 64 received placebo (<16 years, n = 43 [67%]). Incidence of TEAEs was generally similar between age groups. The frequency (per 28 days) of tonic-atonic seizures was reduced with rufinamide (vs. placebo) in both younger and older patients: age <16 years (-41% vs. -6%), age ≥16 years (-55% vs. +16%) (p < 0.025; both age groups). In patients aged <16 years receiving rufinamide, 38% and 17% achieved ≥50% and ≥75% reductions in tonic-atonic seizure frequency vs. 18% and 3% with placebo, respectively. Corresponding responder rates for patients aged ≥16 years were 52% and 32% (rufinamide) vs. 15% and 5% (placebo), respectively. CONCLUSIONS: In this post hoc analysis, adjunctive rufinamide was well tolerated and improved seizure control in patients with LGS, irrespective of age.

A global analysis of the impact of COVID-19 stay-at-home restrictions on crime.

The stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial.

OBJECTIVE/BACKGROUND: Lemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2). PATIENTS/METHODS: Study 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: For all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache. CONCLUSIONS: LEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Comparison of the effect of lemborexant with placebo and zolpidem tartrate extended release on sleep architecture in older adults with insomnia disorder.

STUDY OBJECTIVES: Changes to sleep architecture that occur as a result of the normal aging process may also exacerbate insomnia in older individuals. Therefore, this study assessed the impact of lemborexant compared with placebo and zolpidem tartrate extended release on objective sleep architecture parameters, as measured by polysomnography, in older adults (ages ≥ 55 years) with insomnia disorder from a phase 3 study. METHODS: Study E2006-G000-304 (SUNRISE 1; NCT02783729) was a global, multicenter, randomized, double-blind, placebo-controlled, active comparator (zolpidem)-controlled, parallel-group study comparing 2 dose levels of lemborexant (5 mg and 10 mg). Sleep architecture was measured using polysomnography. Assessments were collected at baseline during a single-blind placebo run-in and during the first 2 nights and last 2 nights of treatment. Mean values for each sleep stage were based on the 2 consecutive polysomnograms. RESULTS: Treatment with lemborexant resulted in significantly greater increases from baseline in total sleep time compared with both placebo and zolpidem. Significant increases from baseline in rapid eye movement sleep and significant decreases from baseline in latency to rapid eye movement sleep were also observed with lemborexant compared with placebo and zolpidem. CONCLUSIONS: These findings suggest that treatment with lemborexant may address some of the alterations in sleep architecture normally observed in older individuals with insomnia. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1); URL: https://clinicaltrials.gov/ct2/show/NCT02783729; Identifier: NCT02783729.

Lack of residual morning effects of lemborexant treatment for insomnia: summary of findings across 9 clinical trials.

OBJECTIVES: Residual next-day effects of sleep-promoting drugs are common and an important safety issue. Lemborexant is a dual orexin receptor antagonist approved in the United States and Japan for treatment of insomnia in adults. We evaluated the potential of lemborexant for residual morning and next-day effects, including somnolence, based on lemborexant clinical study findings. METHODS: This paper reports findings from 9 lemborexant clinical studies that incorporated next-day assessments of residual drug effects, based on published findings and data on file. Results are reported for healthy subjects or subjects with insomnia disorder treated with lemborexant 5 mg/day or 10 mg/day, placebo, or active comparator before bedtime. Outcomes assessed included next-morning postural stability (body sway measured by ataxiameter), cognitive performance (Cognitive Performance Assessment Battery), impact on driving (standard deviation of lateral position during highway driving test), subjective sleepiness (sleep diary entries), and adverse events of somnolence. RESULTS: Change from baseline in postural stability the morning after lemborexant administration did not differ from placebo. Among 4 Cognitive Performance Assessment Battery measures, only power of attention declined significantly more with lemborexant treatment compared with placebo in 1 of 2 studies, whereas zolpidem differed from placebo on multiple measures. On the highway-driving test, lemborexant did not significantly impair driving performance versus placebo, however, zopiclone did differ. In large phase 3 trials, next-morning sleep diary ratings showed significantly greater alertness with lemborexant compared with placebo after up to 6 months of treatment. As expected, somnolence was the most common adverse event reported with lemborexant treatment. Somnolence was typically mild to moderate in severity and rarely caused discontinuation of study drug. CONCLUSION: Across 9 clinical studies, lemborexant did not substantially impair next-day functioning among healthy subjects and subjects with insomnia.

Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2.

STUDY OBJECTIVES: To assess long-term efficacy and safety of lemborexant (LEM), a novel dual orexin receptor antagonist, versus placebo in adults with insomnia disorder. METHODS: This was a 12-month, global, multicenter, randomized, double-blind, parallel-group phase 3 study comprising a 6-month placebo-controlled period (reported here) followed by a 6-month active-treatment-only period (reported separately). A total of 949 participants with insomnia (age ≥18 years) were randomized, received treatment with an oral dose of placebo or LEM (5 mg [LEM5] or 10 mg [LEM10]) and were analyzed. Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored throughout the study. RESULTS: Decreases from baseline in patient-reported (subjective) sleep onset latency and subjective wake after sleep onset, and increases from baseline in subjective sleep efficiency, were significantly greater with LEM5 and LEM10 versus placebo. Significant benefits over placebo were observed at the end of month 6, and at most time points assessed over the 6-month period, indicating long-term sustained efficacy of LEM. A significantly greater percentage of sleep onset responders and sleep maintenance responders were observed with LEM treatment versus placebo. Participants treated with LEM reported a significant improvement in quality of sleep after 6 months versus placebo. The majority of TEAEs were mild or moderate. There was a low rate of serious TEAEs and no deaths. CONCLUSIONS: LEM5 and LEM10 provided significant benefit on sleep onset and sleep maintenance in individuals with insomnia disorder versus placebo, and was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Spontaneous splenic rupture in a patient with chronic myeloid leukemia: A case report.

INTRODUCTION: Spontaneous splenic rupture is an atraumatic event that represents a rare and life-threatening acute complication in which the spleen is damaged producing internal hemorrhage in the abdominal cavity. Its association with hematologic malignancies, although a rare occurrence, has been previously described. Among this subset of patients, chronic myeloid leukemia is one of the main causes. PRESENTATION OF CASE: A 26-year-old male with history of chronic myeloid leukemia presented with acute intense abdominal right lower quadrant pain. Computed tomography showed a wedge in the lower third of the spleen (probably associated with infarction), active bleeding, and hemoperitoneum. Laparotomy and splenectomy were performed. DISCUSSION: The most common symptom of spontaneous splenic rupture is acute abdominal pain, sometimes radiating to the left shoulder. It can also be associated with nausea, emesis and signs of hypovolemia or shock. Splenomegaly may be absent. Diagnostic methods of choice are computed tomography and ultrasound. Management of splenic rupture is divided in surgical and conservative. The former is reserved for patients with extensive splenic injury that is accompanied by hemodynamic instability or other trauma that warrants surgical treatment. Patients who do not meet these criteria and respond to initial stabilization strategies can be offered clinical and laboratory monitoring. Stable patients with moderate to severe splenic injuries can be offered angioembolization. CONCLUSION: It is important to include splenic rupture as a differential diagnosis for acute abdominal pain, especially in patients with hematologic malignancy, since early recognition and treatment increases patient survival and improves prognosis.

Novel seizure outcomes in patients with Lennox-Gastaut syndrome: Post hoc analysis of seizure-free days in rufinamide Study 303.

OBJECTIVE: Drug development for patients with Lennox-Gastaut syndrome (LGS) is based on clinical trials that use drop seizure counts. However, such counts do not assess total seizure burden and affect a patient's quality of life (QoL). In this post hoc analysis, we evaluated two novel seizure efficacy parameters related to QoL in pediatric patients with LGS, using seizure diary data from rufinamide Study 303 (NCT01405053). METHODS: Study 303 was a phase III, multicenter, randomized, controlled, open-label study involving patients aged ≥1 to <4 years with inadequately controlled LGS. Patients were randomized 2:1 to receive add-on therapy with rufinamide or any other approved antiseizure drug (ASD), in addition to their existing treatment of 1-3 ASDs, across a 106-week treatment phase. Seizure diaries, completed by parents or caregivers, recorded seizure occurrence, and were used in this post hoc analysis to evaluate two novel efficacy parameters comparing baseline vs postbaseline mean number of seizure-free days and assessing time to reach the number of prerandomization seizures for patients receiving rufinamide or any other ASD. RESULTS: Patients received rufinamide (n = 25) or any other ASD (n = 12). For rufinamide, mean number of seizure-free days was 42.2% greater postbaseline compared with baseline (P < 0.0001); only one rufinamide patient experienced a decrease in number of seizure-free days postbaseline. Median time to reach the baseline number of seizures increased by 10.5 days for rufinamide and 0.5 days for the any-other-ASD group during the treatment phase, to 46.0 and 54.0 days, respectively. SIGNIFICANCE: Both of these novel and contrasting endpoints demonstrated potential improvements in seizure outcomes in patients receiving rufinamide postbaseline vs baseline. Although these parameters should be investigated in larger patient populations, our initial findings suggest that they could be applied as predefined primary endpoints for seizure assessment in future clinical trials for LGS drug development.

Parámetros genéticos para características de crecimiento, canal, calidad y espinas intramusculares en cachama blanca (Piaractus brachypomus) / Genetic parameters for growth, carcass, quality and intramuscular spine traits in white blanca (Piaractus brachypomus)

RESUMEN Los temas de la acuicultura en los que se requiere innovación e investigación están orientados al mejoramiento y al conocimiento genético de especies nativas. En este sentido, el presente estudio se concentró en estimar heredabilidades, correlaciones genéticas y fenotípicas para características de crecimiento, canal, calidad y espinas intramusculares derechas (EIMD), en cachama blanca (Piaractus brachypomus). La progenie de 12 hembras y 24 machos por fertilización artificial de una hembra por dos machos, es decir, doce familias de hermanos medios, fueron analizados por medio del paquete estadístico SAS 9.4 (SAS®, 2014). Se asumió un modelo lineal general univariado, con inclusión de los efectos fijos, como factores de entorno, estanque y edad y factores genéticos, como efectos aleatorios. Las heredabilidades, en general, para las variables de crecimiento, mostraron valores de medios a altos; para las variables de la canal presentaron valores bajos a medios; para las variables de calidad fueron bajos y, de particular interés para la EIMD, la magnitud de la estima fue de 0,11 ± 0,15. Las correlaciones estuvieron, generalmente, cercanas a la unidad entre características de crecimiento. Estas fueron significativamente positivas para peso corporal, a 180 días de edad, con la mayoría de variables, a diferencia con las variables de calidad, la correlación para rendimiento en canal con EIMD de -0,99 fue encontrada significativamente negativa. Los resultados del estudio destacan el potencial para mejorar características de crecimiento, de canal y de calidad, a través de la explotación de la variación genética aditiva observada.

ABSTRACT The topics of aquaculture in which innovation and research are required are directed towards the improvement and genetic knowledge of native species. In this sense the present study concentrated on the estimation of heritabilities, genetic and phenotypic correlations for growth, carcass, quality and right intramuscular spines (RIMS) in white cachama (Piaractus brachypomus). The progeny of 12 females and 24 males by artificial fertilization of a female by two males, that is to say twelve half-sib families, were analyzed by means of the statistical package SAS 9.4 (SAS®, 2014), assumed an univariate general linear model with inclusion of Fixed effects such as environmental factors, pond and age as fixed effects and genetic factors as random effects. Heritabilities in general for growth variables showed medium to high values; for carcass variables, presented low to medium values; And for the quality variables were low; For the RIMS the magnitude of the estimate was 0,11 ± 0,15. The correlations were generally close to unity between growth characteristics. These were significantly positive for body weight at 180 days of age with most variables unlike quality variables; the correlation for channel performance with RIMS of -0.99 was found to be significantly negative. The results of the study highlight the potential to improve growth, carcass and quality traits through the exploitation of the additive genetic variation observed in this study.

Differentiating pasture honey from eucalyptus honey based on carbon isotopic data in Uruguay.

To avoid false declarations of geographic and botanical honey origin, traceability should be based on analytical data, which could then be processed by multivariate statistical methods. Obtaining this data, however, is costly and time consuming. Thus, it would be more convenient to acquire this information from routine trials, for example from the analysis for determination of high fructose corn syrup (HFCS) concentration in honey. The availability of a procedure of this kind in Uruguay would be useful in discriminating between honeys from grasslands to that from eucalyptus, the two main floral sources for commercial production. To this effect, honey samples (47 from pastures and 42 from eucalypts) were analyzed for δ13C in both honey and its protein fraction. We identified a logistic regression model that allowed us to correctly assign 90% of the training samples, using δ13C data of honey, protein fraction, and the isotopic index as variables. This model was then validated, obtaining 100% correct allocation for honeys from pasture and 90% for honeys from eucalyptus. Moreover, we found that this information could also be used to establish adulteration with HFCS based on a local stricter cut-off limit than that of -1.0‰ of the international index.

Characterisation of Uruguayan Honeys by Multi-Elemental Analyses as a Basis to Assess Their Geographical Origin.

In this work, we evaluated the possibility of predicting the geographic origin of Uruguayan honeys using discriminant analysis (DA) on mineral concentration. Although the DA results appeared to discriminate between honeys from the south, central and north, the subsequent cross-validation analysis did not confirm this result. We also compared honeys from Uruguay and the Buenos Aires province (Argentina) using DA on mineral composition data. In this case, a clear difference between these two origins was observed. It seems possible to differentiate between Uruguayan honeys and those produced in a neighbouring country based on multivariate statistical methods.