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The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM. [ABSTRACT FROM AUTHOR]

Ideophones – imitative words using the stream of speech to simulate/depict the rise and fall of sensory perceptions and emotions and temporal experiences of completiveness, instantaneousness, and repetitiveness – have been characterized as semantically empty and context-dependent. The research reported here tested a simple schematic for the semantic categories of Pastaza Kichwa ideophones by tracking neurological responses to ideophones categorized as VISUAL, MOTION, and SOUND. Seventeen native speakers of Pastaza Kichwa listened to audio clips of ideophones extracted from sentential contexts. Subjects' neural activity was assessed using functional near-infrared spectroscopy. Results demonstrate that these posited semantic categories activate areas of the brain associated with visualization, motion, and sound processing and production, respectively. This suggests that these ideophones convey semantic information related to these concepts, independent of context. This contrasts with what would be expected by theories suggesting that ideophones on their own are semantically empty. The data give rise to questions regarding whether any language contains only sound ideophones that do not carry additional sensory information and whether ideophones in previous studies treated strictly as sound ideophones might require greater specification of their semantics, specifically from a multisensorial perspective. [ABSTRACT FROM AUTHOR]

The recent simulation-based inference (SBI) movement in algebra-based introductory statistics courses (Stat 101) has provided preliminary evidence of improved student conceptual understanding and retention. However, little is known about whether these positive effects are preferentially distributed across types of students entering the course. We consider how two metrics of Stat 101 student preparation (precourse performance on concept inventory and math ACT score) may or may not be associated with end of course student performance on conceptual inventories. Students across all preparation levels tended to show improvement in Stat 101, but more improvement was observed across all student preparation levels in early versions of a SBI course. Furthermore, students' gains tended to be similar regardless of whether students entered the course with more preparation or less. Recent data on a sample of students using a current version of an SBI course showed similar results, though direct comparison with non-SBI students was not possible. Overall, our analysis provides additional evidence that SBI curricula are effective at improving students' conceptual understanding of statistical ideas postcourse regardless student preparation. Further work is needed to better understand nuances of student improvement based on other student demographics, prior coursework as well as instructor and institutional variables.

Stereotactic radiation therapy yields high rates of local control for brain metastases, but patients in rural or suburban areas face geographic and socioeconomic barriers to its access. We conducted a phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases in an integrated academic satellite network for patients 18 years of age or older with 4 or fewer brain metastases. Dose was based on gross tumor volume: less than 3.0 cm, 27 Gy in 3 fractions and 3.0 to 3.9 cm, 30 Gy in 5 fractions. Median follow-up was 10 months for 73 evaluable patients, with a median age of 68 years. Median intracranial progression-free survival was 7.1 months (95% confidence interval = 5.3 to not reached), and median survival was 7.2 months (95% confidence interval = 5.4 to not reached); there were no serious adverse events. Outcomes of this trial compare favorably with contemporary trials, and this treatment strategy provides opportunities to expand stereotactic radiation therapy access to underserved populations. [ABSTRACT FROM AUTHOR]

Previous research suggests that a randomization-based introductory statistics course may improve student learning compared to the consensus curriculum. However, it is unclear whether these gains are retained by students post-course. We compared the conceptual understanding of a cohort of students who took a randomization-based curriculum (n = 76) to a cohort of students who used the consensus curriculum (n = 79). Overall, students taking the randomization-based curriculum showed higher conceptual retention in areas emphasized in the curriculum, with no significant decrease in conceptual retention in other areas. This study provides additional support for the use of randomization-methods in teaching introductory statistics courses. (Contains 2 tables.)

The algebra-based introductory statistics course is the most popular undergraduate course in statistics. While there is a general consensus for the content of the curriculum, the recent Guidelines for Assessment and Instruction in Statistics Education (GAISE) have challenged the pedagogy of this course. Additionally, some arguments have been made that the curriculum should focus on a randomization approach to statistical inference instead of using asymptotic tests. We developed a preliminary version of a randomization based curriculum which we then implemented with 240 students in eight sections of introductory statistics in fall 2009. The Comprehensive Assessment of Outcomes in Statistics (CAOS) assessment test was administered to these students and showed that students learned significantly more about statistical inference using the new curriculum, with comparable learning on most other questions. The assessment results demonstrate that refining content, improving pedagogy and rethinking the consensus curriculum can significantly improve student learning. We will continue to refine both content and pedagogy resulting in improved student learning gains on CAOS items and other assessment measures. (Contains 1 figure and 6 tables.)

Sentinel lymph node biopsy (SLNB) is the preferred method of staging the axilla in patients with early-stage breast cancer. The American Society of Clinical Oncology (ASCO) guidelines recognize SLNB as [...], Background: Completion axillary lymph node dissection (CALND) is recommended in the setting of positive sentinel lymph node biopsy (SLNB) but is associated with a higher rate of postoperative complications. In this study, the characteristics and outcomes of patients who did and did not have CALND are compared. Methods: We identified all patients with breast cancer with positive sentinel lymph nodes (SLNs) who did not have concurrent CALND from 2003 to 2006 using a prospectively collected database (British Columbia Cancer Breast Outcomes database) and retrospective chart review. Patient and tumour characteristics were compared between those who received CALND and those who did not. Results: Among 185 patients with positive SLNs identified by SLNB, 90 had a CALND and 95 had no further surgical therapy. Patients who did not receive CALND had more sentinel nodes removed (p < 0.001), a lower percentage of positive SLNs (p < 0.001) and lower pathologic N stage (p = 0.044) than those who did receive CALND. The size of the breast lesion, size of the largest SLN deposit, estrogen receptor status, grade, lymphovascular invasion, histology and multifocality were not significantly different between groups. Sixty-two percent of women who did not have CALND received radiation to the axilla. Postoperative complication rates (including lymphedema) were higher in the CALND group (21%) compared with the SLNB group (7%). The rates of locoregional recurrence (1% in both groups) and systemic metastases (6% in the CALND group v. 8% in the SLNB group) were similar at 36 months&apos; follow-up. Conclusion: Compared with women who had CALND, women who did not receive CALND had on average a lower N stage with 3 or more SLNs removed and less than 50% node positivity. Most of these women received radiation therapy to the axilla and had comparable recurrence rates to those who had CALND. Contexte : L&apos;ablation des ganglions lymphatiques axillaires (AGLA) est recommandee lorsque la biopsie des ganglions lymphatiques sentinelles donne des resultats positifs, mais cette intervention est associee a un taux plus eleve de complications postoperatoires que la seule biopsie. Cette etude a compare les caracteristiques et les resultats chez les patientes qui ont subi une AGLA et chez celles qui n&apos;ont pas subi cette intervention. Methodes : Nous avons repere toutes les patientes atteintes de cancer du sein chez lesquelles la biopsie des ganglions lymphatiques sentinelles a donne un resultat positif et qui n&apos;avaient pas subi une AGLA simultanee, de 2003 a 2006, a partir d&apos;une base de donnees recueillies de facon prospective (base de donnees sur l&apos;issue du cancer du sein en Colombie-Britannique) et nous avons effectue une etude retrospective des dossiers. Nous avons compare les caracteristiques des patientes et celles de la tumeur chez les patientes qui ont subi une AGLA et chez celles qui n&apos;en ont pas subi. Resultats : Sur les 185 patientes dont les ganglions lymphatiques sentinelles avaient ete juge positif a la suite d&apos;une biopsie, 90 avaient subi une AGLA et 95 n&apos;avaient pas subi d&apos;autre traitement chirurgical. Les patientes qui n&apos;ont pas subi une AGLA avaient subi l&apos;ablation d&apos;un plus grand nombre de ganglions sentinelles (p < 0,001), presentaient un pourcentage moins eleve de ganglions sentinelles positifs (p < 0,001) et se trouvaient a un stade pathologique N moins eleve (p = 0,044) que celles qui ont subi une AGLA. Il n&apos;y avait pas de differences significatives entre les groupes quand a la grosseur de la lesion du sein, a la taille de la concentration la plus importante dans les ganglions lymphatiques sentinelles, a l&apos;etat des recepteurs de l&apos;oestrogene, au grade, a l&apos;envahissement lymphovasculaire, a l&apos;histologie et a la multifocalite. Soixante-deux pour cent des femmes qui n&apos;ont pas subi d&apos;AGLA ont recu une irradiation de l&apos;aisselle. Les taux de complications postoperatoires (y compris de lymphoedeme) ont ete plus eleves chez les patientes qui ont subi une AGLA (21 %) que chez celles qui ont subi une biopsie des ganglions lymphatiques sentinelles (7 %). Les taux de recidive locoregionale (1 % dans les 2 groupes) et de metastases generalisees (6 % chez les patientes qui ont subi une AGLA c. 8 % chez celles qui ont eu une biopsie des ganglions lymphatiques sentinelles) etaient semblables au suivi a 36 mois. Conclusion : Chez les femmes qui n&apos;ont pas subi d&apos;AGLA, par rapport aux femmes qui ont subi cette intervention, le stade N etait en moyenne moins eleve, elles ont subi l&apos;ablation de 3 ganglions lymphatiques sentinelles ou plus et moins de 50 % des ganglions etaient positifs. La plupart de ces femmes ont recu une radiotherapie a l&apos;aisselle et leurs taux de recidive etaient comparables a ceux que l&apos;on a constates chez celles qui avaient subi une AGLA.

Laparoscopic splenectomy was first reported by Delaitre and Maignien in 1991. (1) This technique was quickly adopted as it resulted in reduced hospital stays and lower complication rates. (2) Despite [...], Background: Multiple techniques for splenectomy are now employed and include open, laparoscopic and hand-assisted laparoscopic splenectomy (HALS). Concerns regarding a purely laparoscopic splenectomy for massive splenomegaly (> 20 cm) arise from potentially longer operative times, higher conversion rates and increased blood loss. The HALS technique offers the potential advantages of laparoscopy, with the added safety of having the surgeon's hand in the abdomen during the operation. In this study, we compared the HALS technique to standard open splenectomy for the management of massive splenomegaly. Methods: We reviewed all splenectomies performed at 5 hospitals in the greater Vancouver area between 1988 and 2007 for multiple demographic and outcome measures. Open splenectomies were compared with HALS procedures for spleens larger than 20 cm. Splenectomy reports without data on spleen size were excluded from the analysis. We performed Student t tests and Pearson x2 statistical analyses. Results: A total of 217 splenectomies were analyzed. Of these, 39 splenectomies were performed for spleens larger than 20 cm. We compared the open splenectomy group (19 patients) with the HALS group (20 patients). There was a 5% conversion rate in the HALS group. Estimated blood loss (375 mL v. 935 mL, p = 0.08) and the mean (and standard deviation [SD]) transfusion rates (0.0 [SD 0.0] units v. 0.8 [SD 1.7] units, p = 0.06) were lower in the HALS group. Length of stay in hospital was significantly shorter in the HALS group (4.2 v. 8.9 d, p = 0.001). Complication rates were similar in both groups. Conclusion: Hand-assisted laparoscopic splenectomy is a safe and effective technique for the management of spleens larger than 20 cm. The technique results in shorter hospital stays, and it is a good alternative to open splenectomy when treating patients with massive splenomegaly. Contexte : Les multiples techniques de splenectomie actuellement utilisees comprennent la splenectomie ouverte, la splenectomie laparoscopique et la splenectomie laparoscopique avec assistance manuelle (SLAM). Les preoccupations soulevees par la splenectomie entierement laparoscopique dans les cas de splenomegalie massive (> 20 cm) sont notamment la duree de l'intervention qui peut etre plus longue, les taux de conversion plus eleves et les pertes de sang plus importantes. La technique SLAM peut conjuguer les avantages de la laparoscopie a une securite accrue, du fait que le chirurgien a la main a l'interieur de l'abdomen au cours de l'intervention. Durant cette etude, nous avons compare la technique SLAM a la splenectomie ouverte ordinaire pour la prise en charge d'une splenomegalie massive. Methodes : Nous avons passe en revue toutes les splenectomies pratiquees a 5 hopitaux de la region metropolitaine de Vancouver entre 1988 et 2007 afin d'effectuer de multiples mesures demographiques et analyses des resultats. Nous avons compare la splenectomie ouverte aux interventions pratiquees par la technique SLAM pour les rates de plus de 20 cm. Nous avons exclu de l'analyse les rapports de splenectomie ne comportant pas de donnees sur les dimensions de la rate. Nous avons effectue un test Student t et une analyse statistique du x2 de Pearson. Resultats: Nous avons analyse au total 217 splenectomies, dont 39 ont ete pratiquees sur des rates de plus de 20 cm. Nous avons compare les patients qui ont subi une splenectomie ouverte (19 patients) a ceux qui ont subi une intervention par la technique SLAM (20 patients). Il y a eu un taux de conversion de 5 % chez les patients traites par la technique SLAM. La perte de sang estimee (375 ml c. 935 ml, p = 0,08) et les taux moyens (et l'ecart-type [ET]) de transfusion (0,0 [ET 0,0] unite c. 0,8 [ET 1,7] unite, p = 0,06) ont ete moins eleves chez les patients traites par la technique SLAM, dont l'hospitalisation a ete beaucoup plus courte (4,2 c. 8,9 j, p = 0,001). Les taux de complications etaient semblables dans les 2 groupes. Conclusion : La splenectomie laparoscopique avec assistance manuelle est une technique sans danger et efficace a utiliser pour la prise en charge des rates de plus de 20 cm. L'utilisation de cette technique permet de raccourcir la duree de l'hospitalisation et constitue une bonne solution de rechange a la splenectomie ouverte dans les cas des patients qui ont une splenomegalie massive.