Search

Background: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. Patients and methods: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan–Meier method. Results: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with ‘major’ uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer ‘minor’ mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. Conclusion: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon–common mutation

Background MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab + carboplatin/etoposide in patients with newly diagnosed, extensive-stage small-cell lung cancer (ES-SCLC). The primary objective is the safety evaluation.Materials and Methods Patients received atezolizumab + carboplatin/etoposide Q3W for 4-6 cycles in the induction phase, followed by atezolizumab maintenance Q3W. We presented the interim analysis on safety (referring to the induction phase) and clinical effectiveness, in all patients (N = 154) and in subgroups that received <= 3 (N = 23), 4 (N = 43), and 5-6 cycles (N = 89) of induction.Results At a median follow-up of 10.5 months, 139 patients (90.3%) discontinued treatment. Serious adverse events occurred in 29.9% of patients overall, and the rate was lower in patients with 5-6 cycles (19.1%) than in those with 4 (34.9%) or <= 3 (63.6%) cycles. Immune-mediated adverse events were reported in 14.9%, 15.7%, 11.6%, and 18.2% of patients, overall and by subgroup, respectively. The median overall survival and progression-free survival were 10.7 and 5.5 months, respectively. Overall, 111 patients (71.6%) had a tumor response.Conclusions Interim results provide further evidences about safety and efficacy profile of atezolizumab + carboplatin/etoposide treatment in a ES-SCLC patient population closer to that observed in clinical practice.Clinical Trial Registration Eudract No. 2019-001146-17, NCT04028050.This analysis is based on interim data from the MAURIS study, an Italian multicenter, phase IIIb ongoing trial to evaluate treatment with atezolizumab plus carboplatin/etoposide in patients with newly diagnosed extensive-stage small-cell lung cancer.

Objectives: To evaluate the effect on quality of life (QOL)of the addition of cisplatin to single-agent chemotherapy in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC)enrolled in two parallel phase 3 trials, MILES-3 and MILES-4. Patients and methods: Advanced NSCLC pts, >70 years old, performance status (PS)0–1, were eligible. Patients were randomly assigned to chemotherapy without or with cisplatin. EORTC QLQ C30 and LC13 questionnaires were planned at baseline, end of cycle 1 and end of cycle 2 in both trials and were used for joint QOL analysis. Trial-specific data including questionnaires at non-shared time-points were used for additional analyses. Intention-to-treat strategy was applied. Analyses were adjusted for baseline QOL, stage, performance status, gender, age, size of centre, trial, histotype and non-platinum companion drug. Results: Overall, 458/531 pts (86%)answered baseline questionnaire and missing rates over treatment were slightly higher among patients receiving cisplatin. Mean change in sore mouth after cycle 2 was worse with cisplatin (P = 0.02). The size of differences between arms was in the small-medium range for peripheral neuropathy and alopecia (0.25 and 0.31 after one and 0.28 and 0.36 after two cycles, respectively)and for nausea/vomiting, sore mouth and dysphagia after two cycles (0.26, 0.38 and 0.25, respectively)always in the direction of worsening with cisplatin. Using a 10% change from baseline as clinically relevant threshold to categorize response, there was no significant difference between the arms. Time to deterioration of sore mouth and alopecia, with progression/death as competitive risk, was shorter with cisplatin (HR 1.72 95%CI 1.02–2.89, P = 0.04 and HR 1.84 95%CI 1.09–3.10, P = 0.02, respectively). Conclusion: The addition of cisplatin to single agent chemotherapy worsens sore mouth and alopecia and does not improve any QOL items in elderly patients with advanced NSCLC.

Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds.

Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds.

Compounds combining dual inhibitory action against FAAH and cyclooxygenase (COX) may be potentially useful analgesics. Here, we describe a novel flurbiprofen analogue, N-(3-bromopyridin-2-yl)-2-(2-fluoro-(1,1'-biphenyl)-4-yl)propanamide (Flu-AM4). The compound is a competitive, reversible inhibitor of FAAH with a Ki value of 13 nM and which inhibits COX activity in a substrate-selective manner. Molecular modelling suggested that Flu-AM4 optimally fits a hydrophobic pocket in the ACB region of FAAH, and binds to COX-2 similarly to flurbiprofen. In vivo studies indicated that at a dose of 10 mg/kg, Flu-AM4 was active in models of prolonged (formalin) and neuropathic (chronic constriction injury) pain and reduced the spinal expression of iNOS, COX-2, and NFκB in the neuropathic model. Thus, the present study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models. These findings underscore the potential usefulness of such dual-action compounds.

Angelica Petrillo,1 Giuseppe Tirino,1 Federica Zito Marino,2 Luca Pompella,1 Rosalaura Sabetta,2 Iacopo Panarese,2 Annalisa Pappalardo,1 Marianna Caterino,1 Anna Ventriglia,1 Maria Maddalena Laterza,1 Floriana Morgillo,1 Michele Orditura,1 Fortunato Ciardiello,1 Renato Franco,2 Ferdinando De Vita1 1Division of Medical Oncology, Department of Precision Medicine, School of Medicine, University of Study of Campania “Luigi Vanvitelli”, Naples 80131, Italy; 2Pathology Unit, University of Study of Campania “Luigi Vanvitelli”, Naples 80138, ItalyCorrespondence: Angelica Petrillo Tel +39-0815666729Email angelic.petrillo@gmail.comFerdinando De Vita Tel +39-0815666713Email ferdinando.devita@unicampania.itPurpose: ATTRACTION-2 trial assessed the role of Nivolumab as a new standard treatment for Asian patients with pretreated metastatic gastric cancer (mGC). The aim of this analysis was to evaluate the safety and efficacy of Nivolumab in a real-life Western population, considering the lack of evidence to date.Patients and Methods: Patients progressed after ≥ 2 chemotherapy regimens and able to receive Nivolumab (3 mg/kg q14) were eligible for the analysis.Results: 16 patients received Nivolumab as third (81.3%) or fourth line (18.7%) from September 2017 to July 2019. The safety was in line with the literature and only one patient discontinued treatment due to persistent hematological toxicity. Overall response rate and disease control rate were 18.7% and 31.2%, respectively. Median duration of response was 5 months. With a median follow-up of 21 months, median OS was 6 months (7, 21 and 22 months in the responders) and median PFS 3 months. PD-L1 and microsatellite status were retrospectively collected in 12 patients. All the major responders were MSI, although no statistically significant difference in OS or PFS was observed according to molecular analysis.Conclusion: Nivolumab is feasible and effective in Western patients with mGC

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Create the perfectly customized system by unleashing the power of Android OS on your embedded deviceAbout This BookUnderstand the system architecture and how the source code is organizedExplore the power of Android and customize the build systemBuild a fully customized Android version as per your requirementsWho This Book Is ForIf you are a Java programmer who wants to customize, build, and deploy your own Android version using embedded programming, then this book is for you.What You Will LearnMaster Android architecture and system designObtain source code and understand the modular organizationCustomize and build your first system image for the Android emulatorLevel up and build your own Android system for a real-world deviceUse Android as a home automation and entertainment systemTailor your system with optimizations and add-onsReach for the stars: look at the Internet of Things, entertainment, and domoticsIn DetailTake a deep dive into the Android build system and its customization with Learning Embedded Android Programming, written to help you master the steep learning curve of working with embedded Android. Start by exploring the basics of Android OS, discover Google's “repo” system, and discover how to retrieve AOSP source code. You'll then find out to set up the build environment and the first AOSP system. Next, learn how to customize the boot sequence with a new animation, and use an Android “kitchen” to “cook” your custom ROM. By the end of the book, you'll be able to build customized Android open source projects by developing your own set of features.Style and approachThis step-by-step guide is packed with various real-world examples to help you create a fully customized Android system with the most useful features available.

Create the perfectly customized system by unleashing the power of Android OS on your embedded deviceAbout This BookUnderstand the system architecture and how the source code is organizedExplore the power of Android and customize the build systemBuild a fully customized Android version as per your requirementsWho This Book Is ForIf you are a Java programmer who wants to customize, build, and deploy your own Android version using embedded programming, then this book is for you.What You Will LearnMaster Android architecture and system designObtain source code and understand the modular organizationCustomize and build your first system image for the Android emulatorLevel up and build your own Android system for a real-world deviceUse Android as a home automation and entertainment systemTailor your system with optimizations and add-onsReach for the stars: look at the Internet of Things, entertainment, and domoticsIn DetailTake a deep dive into the Android build system and its customization with Learning Embedded Android Programming, written to help you master the steep learning curve of working with embedded Android. Start by exploring the basics of Android OS, discover Google's “repo” system, and discover how to retrieve AOSP source code. You'll then find out to set up the build environment and the first AOSP system. Next, learn how to customize the boot sequence with a new animation, and use an Android “kitchen” to “cook” your custom ROM. By the end of the book, you'll be able to build customized Android open source projects by developing your own set of features.Style and approachThis step-by-step guide is packed with various real-world examples to help you create a fully customized Android system with the most useful features available.

Create the perfectly customized system by unleashing the power of Android OS on your embedded deviceAbout This BookUnderstand the system architecture and how the source code is organizedExplore the power of Android and customize the build systemBuild a fully customized Android version as per your requirementsWho This Book Is ForIf you are a Java programmer who wants to customize, build, and deploy your own Android version using embedded programming, then this book is for you.What You Will LearnMaster Android architecture and system designObtain source code and understand the modular organizationCustomize and build your first system image for the Android emulatorLevel up and build your own Android system for a real-world deviceUse Android as a home automation and entertainment systemTailor your system with optimizations and add-onsReach for the stars: look at the Internet of Things, entertainment, and domoticsIn DetailTake a deep dive into the Android build system and its customization with Learning Embedded Android Programming, written to help you master the steep learning curve of working with embedded Android. Start by exploring the basics of Android OS, discover Google's “repo” system, and discover how to retrieve AOSP source code. You'll then find out to set up the build environment and the first AOSP system. Next, learn how to customize the boot sequence with a new animation, and use an Android “kitchen” to “cook” your custom ROM. By the end of the book, you'll be able to build customized Android open source projects by developing your own set of features.Style and approachThis step-by-step guide is packed with various real-world examples to help you create a fully customized Android system with the most useful features available.

RxJava—Reactive Extensions for the JVM—is a library for composing asynchronous and event-based programs using Observable sequences for the Java VM, which will help you beat Android platform limitations to create astonishing Android apps.Starting with some quick background information on the Rx .NET library, this book quickly moves on to your first example. You will understand Observables and learn to filter, transform, or merge them in detail. Next, you will learn how to get rid of Threads, AsyncTasks, and Handlers with Schedulers to create a smooth user experience. Develop an easy, ready-to-go approach to REST API communications and enrich your skills by working with new challenging examples.By the end of the book, you will have explored the reactive programming world and will have created your first Android app without having to think about threading, networking, concurrency, and collection management.

RxJava—Reactive Extensions for the JVM—is a library for composing asynchronous and event-based programs using Observable sequences for the Java VM, which will help you beat Android platform limitations to create astonishing Android apps.Starting with some quick background information on the Rx .NET library, this book quickly moves on to your first example. You will understand Observables and learn to filter, transform, or merge them in detail. Next, you will learn how to get rid of Threads, AsyncTasks, and Handlers with Schedulers to create a smooth user experience. Develop an easy, ready-to-go approach to REST API communications and enrich your skills by working with new challenging examples.By the end of the book, you will have explored the reactive programming world and will have created your first Android app without having to think about threading, networking, concurrency, and collection management.

+ ID der Publikation: unilu_51660 + Sprache: Englisch + Letzte Aktualisierung: 2021-04-28 12:27:35

Background: Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children`s hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce. Lack of resources and prescriber opposition are reported barriers. A leadership style focusing on empowering frontline staff to take responsibility is one approach to implement changes in health care institutions. Aim: Literature review regarding empowering leadership and AMS in health care and assessment of the impact of such a leadership style on AMS in a NICU/PICU over 3 years. Methods: Assessment of the impact of a leadership change September 1, 2015 from control-driven to an empowering leadership style on antibiotic use and hospital acquired infections. Prospective analysis and annual comparison of antibiotic use, rate of suspected and confirmed ventilator-associated pneumonia (VAP) and central-line associated blood stream infection (CLABSI) including antibiotic use overall, antibiotic therapy for culture-negative and culture-proven infections including correct initial choice and streamlining of antibiotics in the NICU/PICU of the Children`s Hospital of Lucerne between January 1, 2015 and December 31, 2017. Results: Five articles were included in the literature review. All five studies concluded that an empowering leadership style may lead to a higher engagement of physicians. Three out of five studies reported improved AMS as reduced rate in hospital-acquired infections and improved prevention of MRSA infections. From 2015 to 2017, antibiotic days overall and antibiotic days for culture-negative situations (suspected infections and prophylaxis) per 1000 patient days declined significantly from 474.1 to 403.9 and from 418.2 to 309.4 days, + ID der Publikation: unilu_39969 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 13:15:55

Background and Aims: Neonatal ventilator associated pneumonia (VAP) is a common nosocomial infection and a frequent reason for empirical antibiotic therapy in NICUs. Nonetheless, there is no international consensus regarding diagnostic criteria and management. In a first step, we analyzed the used diagnostic criteria, risk factors and therapeutic management of neonatal VAP by a literature review. In a second step, we aimed to compare suspected vs. confirmed neonatal VAP episodes in our unit according to different published criteria and to analyze interrater-reliability of chest x-rays. Additionally, we aimed to evaluate the development of VAP incidence and antibiotic use after implementation of multifaceted quality improvement changes regarding antimicrobial stewardship and infection control (VAP-prevention-bundle, early-extubation policy, antimicrobial stewardship rounds). Methods: Neonates until 44 weeks of gestation with suspected VAP, hospitalized at our level-III NICU in Lucerne from September 2014 to December 2017 were enrolled. VAP episodes were analyzed according to 4 diagnostic frameworks. Agreement regarding chest x-ray interpretation done by 10 senior physicians was assessed. Annual incidence of suspected and confirmed neonatal VAP episodes and antibiotic days were calculated and compared for the years 2015, 2016, and 2017. Results: 17 studies were identified in our literature review. Overall, CDC-guidelines or similar criteria, requesting radiographic changes as main criteria, are mostly used. Comparison of suspected vs. confirmed neonatal VAP episodes showed a great variance (20.4 vs. 4.5/1,000 ventilator-days). The interrater-reliability of x-ray interpretation was poor (intra-class correlation 0.25). Implemented changes resulted in a gradual decline in annual VAP incidence and antibiotic days from 2015 compared with 2017 (28.8 vs. 7.4 suspected episodes/1,000 ventilator-days, 5.5 vs. 0 confirmed episodes/1,000 ventilator-days and 211 vs. 34.7 antibiot, + ID der Publikation: unilu_39967 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 12:05:30

Background and Aims: Neonatal ventilator associated pneumonia (VAP) is a common nosocomial infection and a frequent reason for empirical antibiotic therapy in NICUs. Nonetheless, there is no international consensus regarding diagnostic criteria and management. In a first step, we analyzed the used diagnostic criteria, risk factors and therapeutic management of neonatal VAP by a literature review. In a second step, we aimed to compare suspected vs. confirmed neonatal VAP episodes in our unit according to different published criteria and to analyze interrater-reliability of chest x-rays. Additionally, we aimed to evaluate the development of VAP incidence and antibiotic use after implementation of multifaceted quality improvement changes regarding antimicrobial stewardship and infection control (VAP-prevention-bundle, early-extubation policy, antimicrobial stewardship rounds). Methods: Neonates until 44 weeks of gestation with suspected VAP, hospitalized at our level-III NICU in Lucerne from September 2014 to December 2017 were enrolled. VAP episodes were analyzed according to 4 diagnostic frameworks. Agreement regarding chest x-ray interpretation done by 10 senior physicians was assessed. Annual incidence of suspected and confirmed neonatal VAP episodes and antibiotic days were calculated and compared for the years 2015, 2016, and 2017. Results: 17 studies were identified in our literature review. Overall, CDC-guidelines or similar criteria, requesting radiographic changes as main criteria, are mostly used. Comparison of suspected vs. confirmed neonatal VAP episodes showed a great variance (20.4 vs. 4.5/1,000 ventilator-days). The interrater-reliability of x-ray interpretation was poor (intra-class correlation 0.25). Implemented changes resulted in a gradual decline in annual VAP incidence and antibiotic days from 2015 compared with 2017 (28.8 vs. 7.4 suspected episodes/1,000 ventilator-days, 5.5 vs. 0 confirmed episodes/1,000 ventilator-days and 211 vs. 34.7 antibiot, + ID der Publikation: unilu_39967 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 12:05:30

Background: Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children`s hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce. Lack of resources and prescriber opposition are reported barriers. A leadership style focusing on empowering frontline staff to take responsibility is one approach to implement changes in health care institutions. Aim: Literature review regarding empowering leadership and AMS in health care and assessment of the impact of such a leadership style on AMS in a NICU/PICU over 3 years. Methods: Assessment of the impact of a leadership change September 1, 2015 from control-driven to an empowering leadership style on antibiotic use and hospital acquired infections. Prospective analysis and annual comparison of antibiotic use, rate of suspected and confirmed ventilator-associated pneumonia (VAP) and central-line associated blood stream infection (CLABSI) including antibiotic use overall, antibiotic therapy for culture-negative and culture-proven infections including correct initial choice and streamlining of antibiotics in the NICU/PICU of the Children`s Hospital of Lucerne between January 1, 2015 and December 31, 2017. Results: Five articles were included in the literature review. All five studies concluded that an empowering leadership style may lead to a higher engagement of physicians. Three out of five studies reported improved AMS as reduced rate in hospital-acquired infections and improved prevention of MRSA infections. From 2015 to 2017, antibiotic days overall and antibiotic days for culture-negative situations (suspected infections and prophylaxis) per 1000 patient days declined significantly from 474.1 to 403.9 and from 418.2 to 309.4 days, + ID der Publikation: unilu_39969 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 13:15:55

Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children's hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce. Lack of resources and prescriber opposition are reported barriers. A leadership style focusing on empowering frontline staff to take responsibility is one approach to implement changes in health care institutions. Literature review regarding empowering leadership and AMS in health care and assessment of the impact of such a leadership style on AMS in a NICU/PICU over 3 years. Assessment of the impact of a leadership change September 1, 2015 from control-driven to an empowering leadership style on antibiotic use and hospital acquired infections. Prospective analysis and annual comparison of antibiotic use, rate of suspected and confirmed ventilator-associated pneumonia (VAP) and central-line associated blood stream infection (CLABSI) including antibiotic use overall, antibiotic therapy for culture-negative and culture-proven infections including correct initial choice and streamlining of antibiotics in the NICU/PICU of the Children's Hospital of Lucerne between January 1, 2015 and December 31, 2017. Five articles were included in the literature review. All five studies concluded that an empowering leadership style may lead to a higher engagement of physicians. Three out of five studies reported improved AMS as reduced rate in hospital-acquired infections and improved prevention of MRSA infections. From 2015 to 2017, antibiotic days overall and antibiotic days for culture-negative situations (suspected infections and prophylaxis) per 1000 patient days declined significantly from 474.1 to 403.9 and from 418.2 to 309.4 days, respectively. Similar, the use of

Background and Aims: Neonatal ventilator associated pneumonia (VAP) is a common nosocomial infection and a frequent reason for empirical antibiotic therapy in NICUs. Nonetheless, there is no international consensus regarding diagnostic criteria and management. In a first step, we analyzed the used diagnostic criteria, risk factors and therapeutic management of neonatal VAP by a literature review. In a second step, we aimed to compare suspected vs. confirmed neonatal VAP episodes in our unit according to different published criteria and to analyze interrater-reliability of chest x-rays. Additionally, we aimed to evaluate the development of VAP incidence and antibiotic use after implementation of multifaceted quality improvement changes regarding antimicrobial stewardship and infection control (VAP-prevention-bundle, early-extubation policy, antimicrobial stewardship rounds). Methods: Neonates until 44 weeks of gestation with suspected VAP, hospitalized at our level-III NICU in Lucerne from September 2014 to December 2017 were enrolled. VAP episodes were analyzed according to 4 diagnostic frameworks. Agreement regarding chest x-ray interpretation done by 10 senior physicians was assessed. Annual incidence of suspected and confirmed neonatal VAP episodes and antibiotic days were calculated and compared for the years 2015, 2016, and 2017. Results: 17 studies were identified in our literature review. Overall, CDC-guidelines or similar criteria, requesting radiographic changes as main criteria, are mostly used. Comparison of suspected vs. confirmed neonatal VAP episodes showed a great variance (20.4 vs. 4.5/1,000 ventilator-days). The interrater-reliability of x-ray interpretation was poor (intra-class correlation 0.25). Implemented changes resulted in a gradual decline in annual VAP incidence and antibiotic days from 2015 compared with 2017 (28.8 vs. 7.4 suspected episodes/1,000 ventilator-days, 5.5 vs. 0 confirmed episodes/1,000 ventilator-days and 211 vs. 34.7, + ID der Publikation: unilu_39967 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 12:05:30

Background: Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children`s hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce. Lack of resources and prescriber opposition are reported barriers. A leadership style focusing on empowering frontline staff to take responsibility is one approach to implement changes in health care institutions. Aim: Literature review regarding empowering leadership and AMS in health care and assessment of the impact of such a leadership style on AMS in a NICU/PICU over 3 years. Methods: Assessment of the impact of a leadership change September 1, 2015 from control-driven to an empowering leadership style on antibiotic use and hospital acquired infections. Prospective analysis and annual comparison of antibiotic use, rate of suspected and confirmed ventilator-associated pneumonia (VAP) and central-line associated blood stream infection (CLABSI) including antibiotic use overall, antibiotic therapy for culture-negative and culture-proven infections including correct initial choice and streamlining of antibiotics in the NICU/PICU of the Children`s Hospital of Lucerne between January 1, 2015 and December 31, 2017. Results: Five articles were included in the literature review. All five studies concluded that an empowering leadership style may lead to a higher engagement of physicians. Three out of five studies reported improved AMS as reduced rate in hospital-acquired infections and improved prevention of MRSA infections. From 2015 to 2017, antibiotic days overall and antibiotic days for culture-negative situations (suspected infections and prophylaxis) per 1000 patient days declined significantly from 474.1 to 403.9 and from 418.2 to 3, + ID der Publikation: unilu_39969 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 13:15:55

Background: Antimicrobial stewardship (AMS) is an important strategy of quality improvement for every hospital. Leadership is an important factor for implementation of quality improvement and AMS programs. Recent publications show successful AMS programs in children`s hospitals, but successful implementation is often difficult to achieve and literature of AMS in neonatal and pediatric intensive care units (NICU/PICU) is scarce. Lack of resources and prescriber opposition are reported barriers. A leadership style focusing on empowering frontline staff to take responsibility is one approach to implement changes in health care institutions. Aim: Literature review regarding empowering leadership and AMS in health care and assessment of the impact of such a leadership style on AMS in a NICU/PICU over 3 years. Methods: Assessment of the impact of a leadership change September 1, 2015 from control-driven to an empowering leadership style on antibiotic use and hospital acquired infections. Prospective analysis and annual comparison of antibiotic use, rate of suspected and confirmed ventilator-associated pneumonia (VAP) and central-line associated blood stream infection (CLABSI) including antibiotic use overall, antibiotic therapy for culture-negative and culture-proven infections including correct initial choice and streamlining of antibiotics in the NICU/PICU of the Children`s Hospital of Lucerne between January 1, 2015 and December 31, 2017. Results: Five articles were included in the literature review. All five studies concluded that an empowering leadership style may lead to a higher engagement of physicians. Three out of five studies reported improved AMS as reduced rate in hospital-acquired infections and improved prevention of MRSA infections. From 2015 to 2017, antibiotic days overall and antibiotic days for culture-negative situations (suspected infections and prophylaxis) per 1000 patient days declined significantly from 474.1 to 403.9 and from 418.2 to 3, + ID der Publikation: unilu_39969 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 13:15:55

Background and Aims: Neonatal ventilator associated pneumonia (VAP) is a common nosocomial infection and a frequent reason for empirical antibiotic therapy in NICUs. Nonetheless, there is no international consensus regarding diagnostic criteria and management. In a first step, we analyzed the used diagnostic criteria, risk factors and therapeutic management of neonatal VAP by a literature review. In a second step, we aimed to compare suspected vs. confirmed neonatal VAP episodes in our unit according to different published criteria and to analyze interrater-reliability of chest x-rays. Additionally, we aimed to evaluate the development of VAP incidence and antibiotic use after implementation of multifaceted quality improvement changes regarding antimicrobial stewardship and infection control (VAP-prevention-bundle, early-extubation policy, antimicrobial stewardship rounds). Methods: Neonates until 44 weeks of gestation with suspected VAP, hospitalized at our level-III NICU in Lucerne from September 2014 to December 2017 were enrolled. VAP episodes were analyzed according to 4 diagnostic frameworks. Agreement regarding chest x-ray interpretation done by 10 senior physicians was assessed. Annual incidence of suspected and confirmed neonatal VAP episodes and antibiotic days were calculated and compared for the years 2015, 2016, and 2017. Results: 17 studies were identified in our literature review. Overall, CDC-guidelines or similar criteria, requesting radiographic changes as main criteria, are mostly used. Comparison of suspected vs. confirmed neonatal VAP episodes showed a great variance (20.4 vs. 4.5/1,000 ventilator-days). The interrater-reliability of x-ray interpretation was poor (intra-class correlation 0.25). Implemented changes resulted in a gradual decline in annual VAP incidence and antibiotic days from 2015 compared with 2017 (28.8 vs. 7.4 suspected episodes/1,000 ventilator-days, 5.5 vs. 0 confirmed episodes/1,000 ventilator-days and 211 vs. 34.7, + ID der Publikation: unilu_39967 + Sprache: Englisch + Letzte Aktualisierung: 2021-03-08 12:05:30

Fatty acid amide hydrolase (FAAH) has a key role in the control of the cannabinoid signaling, through the hydrolysis of the endocannabinoids anandamide and in some tissues 2-arachidonoylglycerol. FAAH inhibition represents a promising strategy to activate the cannabinoid system, since it does not result in the psychotropic and peripheral side effects characterizing the agonists of the cannabinoid receptors. Here we present the discovery of a novel class of profen derivatives, the N-(heteroary1)-2-(4(2-(trifluoromethyl)pyridin-4-y0amino)phenyl)propanamides, as FAAH inhibitors. Enzymatic assays showed potencies toward FAAH ranging from nanomolar to micromolar range, and the most compounds lack activity toward the two isoforms of cyclooxygenase. Extensive structure-activity studies and the definition of the binding mode for the lead compound of the series are also presented. Kinetic assays in rat and mouse FAAH on selected compounds of the series demonstrated that slight modifications of the chemical structure could influence the binding mode and give rise to competitive (TPA1) or noncompetitive (TPA14) inhibition modes.

Small-cell lung cancer (SCLC) represents similar to 15% of all cases of lung cancer and is characterized by a rapid tumour doubling time, early onset disease dissemination and high sensitivity to chemotherapy. We searched MEDLINE and OVID databases for articles in English published from January 1980 to February 2015. Platinum-based chemotherapy, thoracic radiotherapy and prophylactic cranial irradiation are standard of care. Benefit from second-line chemotherapy is limited. The role of platinum/irinotecan chemotherapy in the Western population and the role of maintenance therapies remain to be established. Knowledge of the biology of SCLC has expanded exponentially and many potential therapeutic targets have been identified. The use of circulating tumour cells can help investigating molecular alterations occurring within tumour cells, understanding drug resistance mechanisms and evaluating new treatments.

Create the perfectly customized system by unleashing the power of Android OS on your embedded deviceAbout This BookUnderstand the system architecture and how the source code is organizedExplore the power of Android and customize the build systemBuild a fully customized Android version as per your requirementsWho This Book Is ForIf you are a Java programmer who wants to customize, build, and deploy your own Android version using embedded programming, then this book is for you.What You Will LearnMaster Android architecture and system designObtain source code and understand the modular organizationCustomize and build your first system image for the Android emulatorLevel up and build your own Android system for a real-world deviceUse Android as a home automation and entertainment systemTailor your system with optimizations and add-onsReach for the stars: look at the Internet of Things, entertainment, and domoticsIn DetailTake a deep dive into the Android build system and its customization with Learning Embedded Android Programming, written to help you master the steep learning curve of working with embedded Android. Start by exploring the basics of Android OS, discover Google's “repo” system, and discover how to retrieve AOSP source code. You'll then find out to set up the build environment and the first AOSP system. Next, learn how to customize the boot sequence with a new animation, and use an Android “kitchen” to “cook” your custom ROM. By the end of the book, you'll be able to build customized Android open source projects by developing your own set of features.Style and approachThis step-by-step guide is packed with various real-world examples to help you create a fully customized Android system with the most useful features available.

Background Combined fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) inhibition is a promising approach for pain-relief. The Flu-AM1 and Ibu-AM5 derivatives of flurbiprofen and ibuprofen retain similar COX-inhibitory properties and are more potent inhibitors of FAAH than the parent compounds. However, little is known as to the nature of their interaction with FAAH, or to the importance of their chirality. This has been explored here. Methodology/Principal Findings FAAH inhibitory activity was measured in rat brain homogenates and in lysates expressing either wild-type or FAAH(T488A)-mutated enzyme. Molecular modelling was undertaken using both docking and molecular dynamics. The (R)-and (S)-enantiomers of Flu-AM1 inhibited rat FAAH with similar potencies (IC50 values of 0.74 and 0.99 mu M, respectively), whereas the (S)-enantiomer of Ibu-AM5 (IC50 0.59 mu M) was more potent than the (R)-enantiomer (IC50 5.7 mu M). Multiple inhibition experiments indicated that both (R)-Flu-AM1 and (S)-Ibu-AM5 inhibited FAAH in a manner mutually exclusive to carprofen. Computational studies indicated that the binding site for the Flu-AM1 and Ibu-AM5 enantiomers was located between the acyl chain binding channel and the membrane access channel, in a site overlapping the carprofen binding site, and showed a binding mode in line with that proposed for carprofen and other non-covalent ligands. The potency of (R)-Flu-AM1 was lower towards lysates expressing FAAH mutated at the proposed carprofen binding area than in lysates expressing wild-type FAAH. Conclusions/Significance The study provides kinetic and structural evidence that the enantiomers of Flu-AM1 and Ibu-AM5 bind in the substrate channel of FAAH. This information will be useful in aiding the design of novel dual-action FAAH: COX inhibitors.

Background Combined fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) inhibition is a promising approach for pain-relief. The Flu-AM1 and Ibu-AM5 derivatives of flurbiprofen and ibuprofen retain similar COX-inhibitory properties and are more potent inhibitors of FAAH than the parent compounds. However, little is known as to the nature of their interaction with FAAH, or to the importance of their chirality. This has been explored here. Methodology/Principal Findings FAAH inhibitory activity was measured in rat brain homogenates and in lysates expressing either wild-type or FAAH(T488A)-mutated enzyme. Molecular modelling was undertaken using both docking and molecular dynamics. The (R)-and (S)-enantiomers of Flu-AM1 inhibited rat FAAH with similar potencies (IC50 values of 0.74 and 0.99 mu M, respectively), whereas the (S)-enantiomer of Ibu-AM5 (IC50 0.59 mu M) was more potent than the (R)-enantiomer (IC50 5.7 mu M). Multiple inhibition experiments indicated that both (R)-Flu-AM1 and (S)-Ibu-AM5 inhibited FAAH in a manner mutually exclusive to carprofen. Computational studies indicated that the binding site for the Flu-AM1 and Ibu-AM5 enantiomers was located between the acyl chain binding channel and the membrane access channel, in a site overlapping the carprofen binding site, and showed a binding mode in line with that proposed for carprofen and other non-covalent ligands. The potency of (R)-Flu-AM1 was lower towards lysates expressing FAAH mutated at the proposed carprofen binding area than in lysates expressing wild-type FAAH. Conclusions/Significance The study provides kinetic and structural evidence that the enantiomers of Flu-AM1 and Ibu-AM5 bind in the substrate channel of FAAH. This information will be useful in aiding the design of novel dual-action FAAH: COX inhibitors.

Background Combined fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) inhibition is a promising approach for pain-relief. The Flu-AM1 and Ibu-AM5 derivatives of flurbiprofen and ibuprofen retain similar COX-inhibitory properties and are more potent inhibitors of FAAH than the parent compounds. However, little is known as to the nature of their interaction with FAAH, or to the importance of their chirality. This has been explored here. Methodology/Principal Findings FAAH inhibitory activity was measured in rat brain homogenates and in lysates expressing either wild-type or FAAH(T488A)-mutated enzyme. Molecular modelling was undertaken using both docking and molecular dynamics. The (R)-and (S)-enantiomers of Flu-AM1 inhibited rat FAAH with similar potencies (IC50 values of 0.74 and 0.99 mu M, respectively), whereas the (S)-enantiomer of Ibu-AM5 (IC50 0.59 mu M) was more potent than the (R)-enantiomer (IC50 5.7 mu M). Multiple inhibition experiments indicated that both (R)-Flu-AM1 and (S)-Ibu-AM5 inhibited FAAH in a manner mutually exclusive to carprofen. Computational studies indicated that the binding site for the Flu-AM1 and Ibu-AM5 enantiomers was located between the acyl chain binding channel and the membrane access channel, in a site overlapping the carprofen binding site, and showed a binding mode in line with that proposed for carprofen and other non-covalent ligands. The potency of (R)-Flu-AM1 was lower towards lysates expressing FAAH mutated at the proposed carprofen binding area than in lysates expressing wild-type FAAH. Conclusions/Significance The study provides kinetic and structural evidence that the enantiomers of Flu-AM1 and Ibu-AM5 bind in the substrate channel of FAAH. This information will be useful in aiding the design of novel dual-action FAAH: COX inhibitors.

Background Combined fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) inhibition is a promising approach for pain-relief. The Flu-AM1 and Ibu-AM5 derivatives of flurbiprofen and ibuprofen retain similar COX-inhibitory properties and are more potent inhibitors of FAAH than the parent compounds. However, little is known as to the nature of their interaction with FAAH, or to the importance of their chirality. This has been explored here. Methodology/Principal Findings FAAH inhibitory activity was measured in rat brain homogenates and in lysates expressing either wild-type or FAAH(T488A)-mutated enzyme. Molecular modelling was undertaken using both docking and molecular dynamics. The (R)-and (S)-enantiomers of Flu-AM1 inhibited rat FAAH with similar potencies (IC50 values of 0.74 and 0.99 mu M, respectively), whereas the (S)-enantiomer of Ibu-AM5 (IC50 0.59 mu M) was more potent than the (R)-enantiomer (IC50 5.7 mu M). Multiple inhibition experiments indicated that both (R)-Flu-AM1 and (S)-Ibu-AM5 inhibited FAAH in a manner mutually exclusive to carprofen. Computational studies indicated that the binding site for the Flu-AM1 and Ibu-AM5 enantiomers was located between the acyl chain binding channel and the membrane access channel, in a site overlapping the carprofen binding site, and showed a binding mode in line with that proposed for carprofen and other non-covalent ligands. The potency of (R)-Flu-AM1 was lower towards lysates expressing FAAH mutated at the proposed carprofen binding area than in lysates expressing wild-type FAAH. Conclusions/Significance The study provides kinetic and structural evidence that the enantiomers of Flu-AM1 and Ibu-AM5 bind in the substrate channel of FAAH. This information will be useful in aiding the design of novel dual-action FAAH: COX inhibitors.

Background Combined fatty acid amide hydrolase (FAAH) and cyclooxygenase (COX) inhibition is a promising approach for pain-relief. The Flu-AM1 and Ibu-AM5 derivatives of flurbiprofen and ibuprofen retain similar COX-inhibitory properties and are more potent inhibitors of FAAH than the parent compounds. However, little is known as to the nature of their interaction with FAAH, or to the importance of their chirality. This has been explored here. Methodology/Principal Findings FAAH inhibitory activity was measured in rat brain homogenates and in lysates expressing either wild-type or FAAH(T488A)-mutated enzyme. Molecular modelling was undertaken using both docking and molecular dynamics. The (R)-and (S)-enantiomers of Flu-AM1 inhibited rat FAAH with similar potencies (IC50 values of 0.74 and 0.99 mu M, respectively), whereas the (S)-enantiomer of Ibu-AM5 (IC50 0.59 mu M) was more potent than the (R)-enantiomer (IC50 5.7 mu M). Multiple inhibition experiments indicated that both (R)-Flu-AM1 and (S)-Ibu-AM5 inhibited FAAH in a manner mutually exclusive to carprofen. Computational studies indicated that the binding site for the Flu-AM1 and Ibu-AM5 enantiomers was located between the acyl chain binding channel and the membrane access channel, in a site overlapping the carprofen binding site, and showed a binding mode in line with that proposed for carprofen and other non-covalent ligands. The potency of (R)-Flu-AM1 was lower towards lysates expressing FAAH mutated at the proposed carprofen binding area than in lysates expressing wild-type FAAH. Conclusions/Significance The study provides kinetic and structural evidence that the enantiomers of Flu-AM1 and Ibu-AM5 bind in the substrate channel of FAAH. This information will be useful in aiding the design of novel dual-action FAAH: COX inhibitors.

The mechanisms of differentiation within the nervous system including proliferation and differentiation, migration cell growth and development of axonal and dendritic synaptic connections. Are fundamental processes that generate a remarkably complex neuronal and, to a large extent, still poorly understood. As drafted by the neurotrophic theory, another important process involved in determining the morphology and physiology of neural "programmed cell death (PCD) or apoptosis, which acts both on different types of neuronal and glial cells (Kuan et al. , 2000; Roth and D'Sa, 2001; Davies, 2003, Buss et al, 2006). Although recently this early stage of cell death is the subject of numerous studies, the cell populations involved, the regulatory mechanisms involved, its scale and its functional implications are still far from being characterized as appropriate. The retina is an easily accessible part of the central nervous system and therefore has become a classic model for studies of neural development and apoptosis (Cepko et al., 1996, Harris 1997, Marquardt and Gruss, 2002; Adler, 2005) . In fact, the visual system, while preserving the intense proliferative activity ontogenetic, passes through a number of significant apoptosis (Cook et al 1998; Biehlmaier et al., 2001; Candal et al., 2005; Alunni et al., 2007) . The development of the olfactory system in vertebrate species studied morphogenetic level requires an intense proliferative activity, as witnessed by strong business PCNAsica (Ino et al., 2000) which tends to decline proceeding with development. Likewise, the olfactory mucosa presents events of apoptosis, but as a pattern appears to differ from those that occur in the eye (Ohsawa1 et al., 2008). Of course for each group of vertebrates on this basic scheme, is part of the variants characteristics that determine a unique pattern of development. The data concerning the differentiation of embryonic olfactory and visual system of vertebrates are uncommon and those c

The mechanisms of differentiation within the nervous system including proliferation and differentiation, migration cell growth and development of axonal and dendritic synaptic connections. Are fundamental processes that generate a remarkably complex neuronal and, to a large extent, still poorly understood. As drafted by the neurotrophic theory, another important process involved in determining the morphology and physiology of neural "programmed cell death (PCD) or apoptosis, which acts both on different types of neuronal and glial cells (Kuan et al. , 2000; Roth and D'Sa, 2001; Davies, 2003, Buss et al, 2006). Although recently this early stage of cell death is the subject of numerous studies, the cell populations involved, the regulatory mechanisms involved, its scale and its functional implications are still far from being characterized as appropriate. The retina is an easily accessible part of the central nervous system and therefore has become a classic model for studies of neural development and apoptosis (Cepko et al., 1996, Harris 1997, Marquardt and Gruss, 2002; Adler, 2005) . In fact, the visual system, while preserving the intense proliferative activity ontogenetic, passes through a number of significant apoptosis (Cook et al 1998; Biehlmaier et al., 2001; Candal et al., 2005; Alunni et al., 2007) . The development of the olfactory system in vertebrate species studied morphogenetic level requires an intense proliferative activity, as witnessed by strong business PCNAsica (Ino et al., 2000) which tends to decline proceeding with development. Likewise, the olfactory mucosa presents events of apoptosis, but as a pattern appears to differ from those that occur in the eye (Ohsawa1 et al., 2008). Of course for each group of vertebrates on this basic scheme, is part of the variants characteristics that determine a unique pattern of development. The data concerning the differentiation of embryonic olfactory and visual system of vertebrates are uncommon and those c

The mechanisms of differentiation within the nervous system including proliferation and differentiation, migration cell growth and development of axonal and dendritic synaptic connections. Are fundamental processes that generate a remarkably complex neuronal and, to a large extent, still poorly understood. As drafted by the neurotrophic theory, another important process involved in determining the morphology and physiology of neural "programmed cell death (PCD) or apoptosis, which acts both on different types of neuronal and glial cells (Kuan et al. , 2000; Roth and D'Sa, 2001; Davies, 2003, Buss et al, 2006). Although recently this early stage of cell death is the subject of numerous studies, the cell populations involved, the regulatory mechanisms involved, its scale and its functional implications are still far from being characterized as appropriate. The retina is an easily accessible part of the central nervous system and therefore has become a classic model for studies of neural development and apoptosis (Cepko et al., 1996, Harris 1997, Marquardt and Gruss, 2002; Adler, 2005) . In fact, the visual system, while preserving the intense proliferative activity ontogenetic, passes through a number of significant apoptosis (Cook et al 1998; Biehlmaier et al., 2001; Candal et al., 2005; Alunni et al., 2007) . The development of the olfactory system in vertebrate species studied morphogenetic level requires an intense proliferative activity, as witnessed by strong business PCNAsica (Ino et al., 2000) which tends to decline proceeding with development. Likewise, the olfactory mucosa presents events of apoptosis, but as a pattern appears to differ from those that occur in the eye (Ohsawa1 et al., 2008). Of course for each group of vertebrates on this basic scheme, is part of the variants characteristics that determine a unique pattern of development. The data concerning the differentiation of embryonic olfactory and visual system of vertebrates are uncommon and those c

Erika Martinelli1, Floriana Morgillo1, Teresa Troiani1, Giampaolo Tortora2, Fortunato Ciardiello11Cattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi e A. Lanzara”, Seconda Università degli Studi di Napoli, Napoli, Italy; 2Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinina, Università di Napoli Federico II, Napoli, ItalyIntroduction: Colorectal cancer is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. Panitumumab (ABX-EGF) is the first fully human monoclonal antibody developed for use in colorectal cancer that targets the extracellular domains of epidermal growth factor receptor.Aims: The goal of this article is to review the published evidence for the use of panitumumab in the treatment of metastatic colorectal cancer to define its therapeutic potential.Evidence review: The major evidence of panitumumab activity in colorectal cancer has appeared in meeting report abstracts. One phase II study in monotherapy, one in combination with chemotherapy, and one phase III study have included only patients with metastatic colorectal cancer.Clinical potential: To date, in phase II clinical studies panitumumab has demonstrated antitumor activity in advanced, refractory colorectal cancer. As monotherapy it resulted in a 10% response rate with 38% of patients having stable disease, and a 36% response rate with 46% stable disease when combined with chemotherapy. A phase III study indicates a clinically significant advantage of panitumumab as third-line monotherapy over best supportive care. Panitumumab appears to have a good tolerability profile, with no m

Research has shown that despite formal education, secondary and tertiary students hold a host of misconceptions about respiration. This exploratory study investigated whether a four phase conceptual change teaching strategy could overcome conceptual problems typically associated with respiration, in a Year 8 science class from a school in Perth, Western Australia. The strategy consisted of a Conceptual Awareness Phase, an Exposition Phase, a Misconception Awareness Phase and an Application Phase. Two-tier multiple choice test items used in previous studies to identify misconceptions about respiration were also used in this study, together with interviews. The encouraging results suggest that the implemented conceptual change strategy was successful in developing in Year 8 students an acceptable scientific conception of respiration, and an awareness that the term 'respiration' is used differently by the lay, medical and scientific communities. The strategy was also found to be successful in reducing the incidence of misconceptions typically associated with respiration. Implications and recommendations for educators, textbook authors and curriculum writers, and the need for future research are discussed.

Research has shown that despite formal education, secondary and tertiary students hold a host of misconceptions about respiration. This exploratory study investigated whether a four phase conceptual change teaching strategy could overcome conceptual problems typically associated with respiration, in a Year 8 science class from a school in Perth, Western Australia. The strategy consisted of a Conceptual Awareness Phase, an Exposition Phase, a Misconception Awareness Phase and an Application Phase. Two-tier multiple choice test items used in previous studies to identify misconceptions about respiration were also used in this study, together with interviews. The encouraging results suggest that the implemented conceptual change strategy was successful in developing in Year 8 students an acceptable scientific conception of respiration, and an awareness that the term 'respiration' is used differently by the lay, medical and scientific communities. The strategy was also found to be successful in reducing the incidence of misconceptions typically associated with respiration. Implications and recommendations for educators, textbook authors and curriculum writers, and the need for future research are discussed.

Research has shown that despite formal education, secondary and tertiary students hold a host of misconceptions about respiration. This exploratory study investigated whether a four phase conceptual change teaching strategy could overcome conceptual problems typically associated with respiration, in a Year 8 science class from a school in Perth, Western Australia. The strategy consisted of a Conceptual Awareness Phase, an Exposition Phase, a Misconception Awareness Phase and an Application Phase. Two-tier multiple choice test items used in previous studies to identify misconceptions about respiration were also used in this study, together with interviews. The encouraging results suggest that the implemented conceptual change strategy was successful in developing in Year 8 students an acceptable scientific conception of respiration, and an awareness that the term 'respiration' is used differently by the lay, medical and scientific communities. The strategy was also found to be successful in reducing the incidence of misconceptions typically associated with respiration. Implications and recommendations for educators, textbook authors and curriculum writers, and the need for future research are discussed.

Research has shown that despite formal education, secondary and tertiary students hold a host of misconceptions about respiration. This exploratory study investigated whether a four phase conceptual change teaching strategy could overcome conceptual problems typically associated with respiration, in a Year 8 science class from a school in Perth, Western Australia. The strategy consisted of a Conceptual Awareness Phase, an Exposition Phase, a Misconception Awareness Phase and an Application Phase. Two-tier multiple choice test items used in previous studies to identify misconceptions about respiration were also used in this study, together with interviews. The encouraging results suggest that the implemented conceptual change strategy was successful in developing in Year 8 students an acceptable scientific conception of respiration, and an awareness that the term 'respiration' is used differently by the lay, medical and scientific communities. The strategy was also found to be successful in reducing the incidence of misconceptions typically associated with respiration. Implications and recommendations for educators, textbook authors and curriculum writers, and the need for future research are discussed.

Research has shown that despite formal education, secondary and tertiary students hold a host of misconceptions about respiration. This exploratory study investigated whether a four phase conceptual change teaching strategy could overcome conceptual problems typically associated with respiration, in a Year 8 science class from a school in Perth, Western Australia. The strategy consisted of a Conceptual Awareness Phase, an Exposition Phase, a Misconception Awareness Phase and an Application Phase. Two-tier multiple choice test items used in previous studies to identify misconceptions about respiration were also used in this study, together with interviews. The encouraging results suggest that the implemented conceptual change strategy was successful in developing in Year 8 students an acceptable scientific conception of respiration, and an awareness that the term 'respiration' is used differently by the lay, medical and scientific communities. The strategy was also found to be successful in reducing the incidence of misconceptions typically associated with respiration. Implications and recommendations for educators, textbook authors and curriculum writers, and the need for future research are discussed.

There have been many tracking studies performed throughout the years in laboratories where a subject is required to track a point on some form of visual display. Very few studies have been performed in the field environment with larger than point type targets. The purpose of this study was to determine the magnitude and distribution of error when tracking the unmarked center of mass of a large diameter circular target and eventually to compare these errors to those found in the tracking of a circular target with a marked aim point at the center of mass. The results show that the distribution of error did change as a function of visual angle. As visual angle increased, the distribution of error tended to change from what appeared to be a uniform distribution to a distribution that had the tendency to peak. This was illustrated in the frequency histograms and verified using the aforementioned statistical tools. The standard deviation of tracking error was approximately 57 percent larger using targets without marked aim points compared to targets with marked aim points. There was a slight decrease in standard deviation of error as targets become larger; however, this trend was not considered significant from a practical point of view.