119 research outputs found
Tumor MGMT promoter hypermethylation changes over time limit temozolomide efficacy in a phase II trial for metastatic colorectal cancer
Chasse et développement territorial. Vers un cadre d’analyse global ?
L’article propose une analyse de la contribution des activités cynégétiques au développement territorial en s’appuyant sur deux cadres théoriques complémentaires. D’une part, une version revisitée de la théorie de la base intégrant "une base de consommation" peut permettre de rendre compte des effets à la fois des chasseurs extérieurs et des chasseurs locaux. D’autre part, la chasse peut être à l’origine d’un processus d’innovation et de spécification des ressources territoriales.The paper proposes an analysis of the contribution of huntings to local development with two complementary theoretical frameworks. On one hand, a revisited version of the economic base models integrating "a consumption base" is able to measure both effects of the external hunters and the local hunters. On the other hand, hunting can generate an innovation process and specification of "territorial resources"
Multi-Determinants Analysis of Molecular Alterations for Predicting Clinical Benefit to EGFR-Targeted Monoclonal Antibodies in Colorectal Cancer
KRAS mutations occur in 35-45% of metastatic colorectal cancers (mCRC) and preclude responsiveness to EGFR-targeted therapy with cetuximab or panitumumab. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been found to give rise to resistance. We present a comprehensive analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression in mCRC patients treated with cetuximab or panitumumab, with the aim of clarifying the relative contribution of these molecular alterations to resistance.We retrospectively analyzed objective tumor response, progression-free (PFS) and overall survival (OS) together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non-responsive patients, 74 (70%) had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43) among patients with no alterations, 4% (2/47) among patients with 1 alteration, and 0% (0/24) for patients with > or =2 alterations (p<0.0001). Accordingly, PFS and OS were increasingly worse for patients with tumors harboring none, 1, or > or =2 molecular alteration(s) (p<0.001).When expression of PTEN and mutations of KRAS, BRAF and PIK3CA are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as 'quadruple negative', the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab-based therapies
Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility : a Single-Institution Experience
BACKGROUND:
Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.
OBJECTIVE:
We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).
PATIENTS AND METHODS:
From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36-86) and the median number of previous treatment lines was five (range 2-8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).
RESULTS:
One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63-3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0-15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80-5.03] vs. 2.13 months [95% CI 1.77-2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17-9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33-10.80] vs. 7.18 months [95% CI 5.63-9.33], respectively, p = 0.06).
CONCLUSIONS:
This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment
Utilizing Paraeducators to Increase Treatment Integrity of Behavior Interventions Through the Use of Performance Feedback
This study implemented performance feedback with paraeducators to increase the treatment integrity of behavior interventions. Treatment integrity, also known as treatment fidelity, refers to the extent to which an intervention is implemented as intended. Currently, performance feedback is the most research supported method for increasing treatment integrity in schools (Fallon, Collier-Meek, Maggin, Sanetti, & Johnson, 2015). Stemming from the organizational psychology literature, performance feedback is a tailored method of ongoing consultation in which a consultant collects data on the integrity of intervention components, as well as a target behavior of the student. By presenting the implementation data alongside student outcomes, the consultee is made aware of the functional relationship between their behavior and that of their students (Mortenson & Witt, 1998). This study targeted paraeducators, as they are becoming more commonly utilized when intervening with students with challenging behaviors (Giangreco, & Broer, 2005). Although they are tasked with this responsibility, paraeducators often do not receive adequate behavioral training and can struggle to implement individualized behavior plans (Giangreco, Hurley, & Suter, 2009). The goal of performance feedback is to provide a short-term intervention to increase both the skill level and the performance of the consultee (paraeducator). The purpose of this study was to determine if there is a functional relationship between performance feedback and treatment integrity of comprehensive behavior intervention plans. Three outcome variables were studied: treatment integrity, student noncompliance and student replacement behavior. Participants included four paraeducator student dyads. Performance feedback occurred once per week until the paraeducator reached 80% mastery across three occasions. Effect size analyses were used in addition to visual analyses. Results showed that a functional relationship between performance feedback and improved treatment integrity for all four participants. Student-level results included a small effect for noncompliance and no effect for replacement behavior. This study provides evidence for the use of performance feedback with paraeducators
Prof, non ho il cambio!
La didattica delle Scienze Motorie implica, più che mai al giorno d'oggi, profonde riflessioni metodologiche e applicative. I riferimenti scientifici e culturali, ovviamente, non devono mai venir meno; tuttavia, è importante che essi vadano di pari passo con la ricerca delle migliori modalità di trasmissione del sapere, del saper fare e del saper essere, affinché possa realizzarsi concretamente un proficuo contributo alla formazione globale della persona, educando il movimento e attraverso il movimento. Pertanto, l'autorevolezza della/del docente richiede costanti attenzioni applicative, riscontrabili nella didattica curricolare quotidiana
Sintesi, caratterizzazione e attività catalitica di complessi carbenici di metalli del gruppo 10 recanti gruppi amminici pendenti
Nel corso di questa Tesi sono stati sintetizzati complessi carbenici di metalli del gruppo 10 (Ni, Pd e Pt) recanti gruppi amminici pendenti.
Per la sintesi di questi composti si è fatto riferimento a procedure sperimentali riportate in letteratura ed effettuando in alcuni casi opportune modifiche.
I prodotti ottenuti sono stati caratterizzati tramite analisi NMR monodimensionale (1H e 13C), bidimensionale e nei casi in cui sono stati ottenuti i cristalli anche tramite diffrazione ai raggi-X.
E’ stata poi verificata l’efficienza catalitica di questi complessi in opportune reazioni in cui la presenza della funzione amminica pendente potesse teoricamente dare un grosso contributo alla catalisi della reazione stessa.
I complessi di Ni(II) e Pt(II) sarebbero dovuti essere testati per la generazione per via elettrochimica di H2 da soluzione acide, ma da analisi elettrochimica (voltammetria ciclica) è stato verificato che questi composti non mostravano un comportamento adeguato per la catalisi di questo tipo di reazione, mentre i complessi di Pd(II), che sono stati utilizzati come catalizzatori delle reazioni di Sonogashira, hanno permesso di ottenere dei risultati buoni e molto promettenti per il futuro
Using Performance Feedback to Increase Treatment Integrity in Behavioral Interventions: Meta-Analysis
This study examined the effects of performance feedback on the treatment integrity of various behavioral interventions occurring inside a classroom setting. Nine studies were analyzed across seven moderator variables (school, classroom, intervention, latency of feedback, type of feedback, consultee position and consultee experience). This meta-analysis was driven by three research questions: a) What is the magnitude of performance feedback on the treatment integrity of behavioral interventions? b) Is performance feedback an effective intervention for more intensive behavioral concerns? c) What factors make performance feedback more beneficial? Major findings in this study included small to large effect sizes, with larger effects seen in special education classrooms and interventions for behavior-specific praise. These findings suggest that performance feedback can be used across school and classroom types as well as to address intensive behavioral concerns
Making sense of schizophrenic symptoms; delusional statements and behavior may be functional in purpose∗
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