Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial

BACKGROUND VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. METHODS In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. FINDINGS Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. INTERPRETATION Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable. FUNDING Eli Lilly and Co.

If we call them, will they change? Feasibility of a telephone adaptation of motivational interviewing aimed at parents to reduce television time among 2nd and 4th grade children

Television viewing is a sedentary behavior that is modifiable. Reducing media-related behaviors via parent-focused interventions may hold promise for decreasing childhood obesity. This feasibility study examines a novel parent-centered brief telephone-delivered Motivational Enhancement Interview (MEI) to encourage parents of 2nd and 4th graders to set a rules limiting TV time or remove the TV from the child's bedroom. This quasi-experimental sub-study was part of the larger CATCH: En Vivo pilot study conducted in a Hispanic population in the Texas Rio Grande Valley. Parents in the MEI condition were contacted via telephone and encouraged to meet the American Academy of Pediatrics (AAP) recommended 2 hours per day or less of TV. Unconditional logistic regression was used to analyze the data. At post-test, 85% of parents of 4th graders in the MEI group (compared to 71% at pre-test) reported having a rule limiting TV time. The adjusted odds ratio for the MEI group compared to the control group was 3.88, 95% CI (0.72-20.99). At pre-test, 63.16% of 2nd graders had a television in their bedrooms. The 2nd grade MEI intervention reduced that number to 41.03% (OR=0.25, 95%CI (0.08-0.82)). This first look at using MEI to target parents of children to modify TV behavior presents evidence on a promising strategy for modifying children's home media environment and warrants further investigation. ^

Boston, Massachusetts Region LIDAR First Return Elevation Data, 2002

LIDAR (LIght Detection And Ranging) first return elevation data of the Boston, Massachusetts region from MassGIS at 1-meter resolution. This LIDAR data was captured in Spring 2002. LIDAR first return data (which shows the highest ground features, e.g. tree canopy, buildings etc.) can be used to produce a digital terrain model of the Earth's surface. This dataset consists of 74 First Return DEM tiles. The tiles are 4km by 4km areas corresponding with the MassGIS orthoimage index. This data set was collected using 3Di's Digital Airborne Topographic Imaging System II (DATIS II). The area of coverage corresponds to the following MassGIS orthophoto quads covering the Boston region (MassGIS orthophoto quad ID: 229890, 229894, 229898, 229902, 233886, 233890, 233894, 233898, 233902, 233906, 233910, 237890, 237894, 237898, 237902, 237906, 237910, 241890, 241894, 241898, 241902, 245898, 245902). The geographic extent of this dataset is the same as that of the MassGIS dataset: Boston, Massachusetts Region 1:5,000 Color Ortho Imagery (1/2-meter Resolution), 2001 and was used to produce the MassGIS dataset: Boston, Massachusetts, 2-Dimensional Building Footprints with Roof Height Data (from LIDAR data), 2002 [see cross references].

Relationships between First Generation College Students and Faculty: A Case Study of a Small Rural Private University

Thesis (Ed.D.)--University of Washington, 2016-06

Factors in the selection of patients for conditional release from their first psychiatric hospitalization

Objective: This study examined a sample of patients in Victoria, Australia, to identify factors in selection for conditional release from an initial hospitalization that occurred within 30 days of entry into the mental health system. Methods: Data were from the Victorian Psychiatric Case Register. All patients first hospitalized and conditionally released between 1990 and 2000 were identified (N = 8,879), and three comparison groups were created. Two groups were hospitalized within 30 days of entering the system: those who were given conditional release and those who were not. A third group was conditionally released from a hospitalization that occurred after or extended beyond 30 days after system entry. Logistic regression identified characteristics that distinguished the first group. Ordinary least-squares regression was used to evaluate the contribution of conditional release early in treatment to reducing inpatient episodes, inpatient days, days per episode, and inpatient days per 30 days in the system. Results: Conditional release early in treatment was used for 11 percent of the sample, or more than a third of those who were eligible for this intervention. Factors significantly associated with selection for early conditional release were those related to a better prognosis ( initial hospitalization at a later age and having greater than an 11th grade education), a lower likelihood of a diagnosis of dementia or schizophrenia, involuntary status at first inpatient admission, and greater community involvement ( being employed and being married). When the analyses controlled for these factors, use of conditional release early in treatment was significantly associated with a reduction in use of subsequent inpatient care.

SCOTROC 2A: Carboplatin followed by docetaxel or docetaxel gemcitabine as first-line chemotherapy for ovarian cancer

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P = 0.102, P = 0.056, P = 0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% Cl: 10.5 - 20.6); arm B 18.1 months (95% Cl: 15.9 - 20.3); arm C, 13.7 months (95% Cl: 12.8 - 14.6). Neutropenia was the predominant grade 3 - 4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P = 0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Readability of selected breastfeeding information for mothers: Early twenty-first centure

The effectiveness of printed material depends on its clarity, layout, and appropriateness of its reading level to the target population. A person with 'functional illiteracy' is able to read at a basic level or below, but is confused by more complex material. Among Australian adults, the estimated functional illiteracy rate for prose is 44.1%. Consequently, it is recommended that health information literature for the general population be pitched at a grade 5 or 6 level of reading difficulty. This study is a ten-year follow-up to an earlier study by the author, which analysed printed information materials from the late twentieth century. The aim was to assess the

The effect of the environment on the mechanical properties of medical grade silicones

Silicone spacers have been in use as replacement joints in the human hand for over 30 years. Since they were first used there has been a number of designs all of which have had problems with fracture. This may be due to a defect in the material caused during implantation, or by bony intrusions within the arthritic hand after implantation. The aim of this research was to investigate the effect of the environment on the mechanical properties of medical grade silicones used for human implantation. The materials were subjected to static tensile testing after various forms of ageing. The environmental conditions included temperatures of 37 and 80°C and the environments of Ringer's solution, distilled water, and air. The environmental conditions employed resulted in reduced mechanical strength with ageing time of the silicones. This research supports the view that failure of silicone implants in the hand could be partly attributed to the effects of environmental ageing of the material.

A fourth-grade teacher's classroom perspective

Countless books have been written about what is good and what is bad about our educational system. No matter what the book or what the theory, all agree the classroom teacher is critical to the education process. Many influences affect classroom teaching, some of which are beyond her control, but a caring classroom teacher has a central role in the instruction of children The purpose of this case study was to inquire into the beliefs and behaviors of one elementary school teacher in a low socio-economic school and study her classroom perspective. This teacher of five years was a reading specialist and was teaching a full fourth grade curriculum for the first time. Because she suffered from math phobia, she was apprehensive about teaching mathematics. ^ This qualitative study required intense, time-consuming interviews, long and frequent observations, critical journaling, field notes and artifacts provided by the teacher. The resulting descriptive data was coded into categories and reassembled into themes that captured the essence of the teacher's beliefs. ^ The overarching themes found were: first, the teacher's caring attitude towards her students, cultivated by her affectionate family, her mother who is an elementary school teacher, and rich and rewarding elementary school experiences, second, her implementation of the curriculum, influenced by her passion for reading, her math phobia, and standardized tests and third, her attitudes toward her workplace, school administrators and collegiality among teachers. During the school year this teacher “owned” her classroom and was a full participant in its life! Her dedication to teaching was fostered by the satisfaction of knowing she has a profound impact and makes a significant difference in her students' lives. ^ This study suggested areas for further research on the following topics: consideration of teachers with math phobia, the effect of standardized tests on areas of the curriculum and the value of computers in the elementary school classroom. ^

The efficacy of the Ellison model as a retention initiative for first semester freshmen

The freshman year is the most critical year of matriculation for students in higher education. One in four freshman students drops out of higher education after the first year. In fact, the first two to six weeks of college represent a very critical transition period when students make the decision to persist or depart from the institution. Many students leave because they are unable to make a connection with the institution. Retention is often profoundly affected by student involvement in the academic environment, satisfaction with the campus climate and the institution's response to diversity. Therefore, the purpose of this study was to examine and evaluate an effective institutional response that promotes freshman retention and academic success. The tenets (diversity training, conflict management, and community building) of a mentoring model were applied to the freshman experience seminar class (experimental group) as a pedagogical method of instruction to determine its efficacy as a retention initiative when compared with the traditional freshman experience seminar class (comparison group). ^ The quantitative study employed a quasi-experimental research design based on Astin's (1993) I-E-O model. The model examined the relationships between the characteristics students bring with them to college, called inputs, their experiences in the environment during college, and the outcomes students achieved during matriculation. Fifty-two students enrolled in the freshman seminar class participated in the study. ^ Demographic data and input variables between groups were analyzed using chi-square, t-tests and multivariate analyses. Overall, students in the experimental group had significantly higher satisfaction (campus climate) scores than the comparison group. An analysis of the students' willingness to interact with others from diverse groups indicated a significant difference between groups, with the experimental group scoring higher than the comparison group. Students in the experimental group were significantly more involved in campus activities than students in the comparison group. No significant differences were found between groups relative to the mean grade point average and re-enrollment for fall semester 2001. ^ While the mentoring model did not directly affect re-enrollment of students, the model did promote student satisfaction with the institution, an appreciation for diversity of contact and it encouraged involvement in the campus community. These are all essential outcomes of a quality retention program. ^

Predictors of first semester attrition and their relation to retention of generic associate degree nursing students

In community college nursing programs the high rate of attrition was a major concern to faculty and administrators. Since first semester attrition could lead to permanent loss of students and low retention in nursing programs, it was important to identify at-risk students early and develop proactive approaches to assist them to be successful. The goal of nursing programs was to graduate students who were eligible to take the national council licensing examination (RN). This was especially important during a time of critical shortage in the nursing workforce. ^ This study took place at a large, multi-campus community college, and used Tinto's (1975) Student Integration Model of persistence as the framework. A correlational study was conducted to determine whether the independent variables, past academic achievement, English proficiency, achievement tendency, weekly hours of employment and financial resources, could discriminate between the two grade groups, pass and not pass. Establishing the relationship between the selected variables and successful course completion might be used to reduce attrition and improve retention. Three research instruments were used to collect data. A Demographic Information form developed by the researcher was used to obtain academic data, the research questionnaire Measure of Achieving Tendency measured achievement motivation, and the Test of Adult Basic Education (TABE), Form 8, Level A, Tests 1, 4, and 5 measured the level of English proficiency. The Department of Nursing academic policy, requiring a minimum course grade of “C” or better was used to determine the final course outcome. A stepwise discriminant analysis procedure indicated that college language level and pre-semester grade point average were significant predictors of final course outcome. ^ Based on the findings of the study recommendations focused on assessing students' English proficiency prior to admission into the nursing program, an intensive remediation plan in language comprehension for at-risk students, and the selection of alternate textbooks and readings that more closely matched the English proficiency level of the students. A pilot study should be conducted to investigate the benefit of raising the admission grade point average. ^

The performance of high -ability Black upper elementary grade students in an International Baccalaureate program

The purpose of this study was to investigate the common factors and experiences that contribute to the success of high ability Black students enrolled in Frank C. Martin Elementary School, the first school in Florida authorized to offer the International Baccalaureate (IB) Primary Years Programme (PYP). The study further sought to determine ways in which educators and stakeholders assisted in maintaining and in increasing Black students' achievement that motivated and encouraged them to pursue similar programs at the middle and high school levels. ^ Three sources of data were used: (a) individual interviews with fourth and fifth grade high ability Black students using a semi-structured format elicited discussion of their perceptions of the PYP and factors contributing to their success; (b) individual interviews with their fourth and fifth grade teachers elicited discussion of teacher expectations and effective instructional strategies; and (c) a questionnaire asked parents of the participating students their reasons for choosing the PYP, their perceptions of the program, and their own level of involvement in their child's learning. Three separate focus groups gathered further data. ^ The results revealed that the factors contributing to the success of high ability Black elementary school students are consistent with those of students in other racial groups. These are a challenging program, high teacher and parental expectations, strong parental involvement and support, a celebration of culture and diversity in a caring and nurturing environment, and the development and internalization of positive attitudes. ^ Implications for future studies might include a longitudinal study conducted over seven years to trace the achievements of Black students throughout the entire IB Program. ^

Effects of sex, third grade reading achievement and motivation as predictors of fourth grade reading achievement of Hispanic students: A path analysis

This study explored the topic of motivation for intermediate students combining both an objective criterion measure (i.e., standardized test scores) and the self-report of students on self-concept and value of reading. The purpose of this study was to examine how third grade reading achievement correlated with the motivation of fourth grade boys and girls, and, in turn, how motivation related to fourth grade reading achievement. The participants were fourth grade students (n=207) attending two public, elementary schools in Miami-Dade County who were of primarily Hispanic origin or descent. Data were collected using the Reading Survey portion of the Motivation to Read Profile (1996) which measures self-concept and value of reading in order to measure motivation and the Third and Fourth Grade Reading Florida Comprehensive Assessment Tests 2.0 (FCAT 2.0) to assess achievement. First, a one way Analysis of Variance (ANOVA) was conducted to determine whether motivation differed significantly between fourth grade boys and girls. Second, a path analysis was used to determine whether motivation mediated or moderated the association between FCAT 2.0 third and fourth grade scores. Results of the ANOVA indicated that motivation, as measured by the Motivation to Read Profile did not differ significantly by sex. Results from the path analysis indicated that the model was significant and that third grade FCAT 2.0 scores accounted for a significant amount of the variance in fourth grade FCAT 2.0 scores once motivation was entered. Results of the study demonstrated that motivation partially mediates, but does not moderate the relationship between FCAT 2.0 third and fourth grade scores. In conclusion, it can be determined that past student achievement for fourth grade students plays a role in current student achievement when motivation is also considered. It is therefore important in order to improve the quality of fourth grade student's current performance to take into account a student's motivation and past achievement. An effort must be made to address students' motivational needs whether through school wide programs or at the classroom level in addition or in conjunction with cognition. Future research on the effect of self-concept in reading achievement is recommended.

The effect of music listening maps on second grade music students' preference for and understanding of orchestral music

This study investigated the use of music listening maps to help learning and the preferences of second graders for orchestral music. Subjects were a population of four 2nd grade classes, and were randomly divided into two groups. The investigation was a counterbalanced, post-test only design, lasting for three consecutive classes. Two treatments/lessons were presented and a third lesson was a review. In Treatment 1 Group I used listening maps first, while Group II received instruction without listening maps. In Treatment 2, the order was reversed. Two post-tests and a comprehensive test were administered. An affective survey was administered after the treatments, measuring student preference and attitude. When listening maps were presented, scores were significantly higher. It did not matter whether the listening maps were presented first or not. Results of the survey show student preference will increase with music listening maps.

Investigating high-achieving sixth grade students' erroneous answers on the angle concept in Yozgat

The angle concept is a multifaceted concept having static and dynamic definitions. The static definition of the angle refers to “the space between two rays” or “the intersection of two rays at the same end point” (Mitchelmore & White, 1998), whereas the dynamic definition of the angle concept highlights that the size of angle is the amount of rotation in direction (Fyhn, 2006). Since both definitions represent two diverse situations and have unique limitations (Henderson & Taimina, 2005), students may hold misconceptions about the angle concept. In this regard, the aim of this research was to explore high achievers’ knowledge regarding the definition of the angle concept as well as to investigate their erroneous answers on the angle concept.

104 grade 6 students drawn from four well-established elementary schools of Yozgat, Turkey were participated in this research. All participants were selected via a purposive sampling method and their mathematics grades were 4 or 5 out of 5, and. Data were collected through four questions prepared by considering the learning competencies set out in the grade 6 curriculum in Turkey and the findings of previous studies whose purposes were to identify students’ misconceptions of the angle concept. The findings were analyzed by two researchers, and their inter-rater agreement was calculated as 0.91, or almost perfect. Thereafter, coding discrepancies were resolved, and consensus was established.

The angle concept is a multifaceted concept having static and dynamic definitions.The static definition of the angle refers to “the space between two rays” or“the intersection of two rays at the same end point” (Mitchelmore & White, 1998), whereas the dynamicdefinition of the angle concept highlights that the size of angle is the amountof rotation in direction (Fyhn, 2006). Since both definitionsrepresent two diverse situations and have unique limitations (Henderson & Taimina, 2005), students may holdmisconceptions about the angle concept. In this regard, the aim of thisresearch was to explore high achievers’ knowledge regarding the definition ofthe angle concept as well as to investigate their erroneous answers on theangle concept.