Multiple gene aberrations and breast cancer: lessons from super-responders.

BackgroundThe presence of multiple molecular aberrations in patients with breast cancer may correlate with worse outcomes.Case presentationsWe performed in-depth molecular analysis of patients with estrogen receptor-positive, HER2-negative, hormone therapy-refractory breast cancer, who achieved partial or complete responses when treated with anastrozole and everolimus. Tumors were analyzed using a targeted next generation sequencing (NGS) assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Patients received anastrozole (1 g PO daily) and everolimus (5 or 10 mg PO daily). Thirty-two patients with breast cancer were treated on study and 5 (16 %) achieved a partial or complete response. Primary breast tissue was available for NGS testing in three of the responders (partial response with progression free survival of 11 and 14 months, respectively; complete response with progression free survival of 9+ months). The following molecular aberrations were observed: PTEN loss by immunohistochemistry, CCDN1 and FGFR1 amplifications, and PRKDC re-arrangement (NGS) (patient #1); PIK3CA and PIK3R1 mutations, and CCDN1, FGFR1, MYC amplifications (patient #2); TP53 mutation, CCNE1, IRS2 and MCL1 amplifications (patient #3). Some (but not all) of these aberrations converge on the PI3K/AKT/mTOR pathway, perhaps accounting for response.ConclusionsPatients with estrogen receptor-positive breast cancer can achieve significant responses on a combination of anastrozole and everolimus, even in the presence of multiple molecular aberrations. Further study of next generation sequencing-profiled tumors for convergence and resistance pathways is warranted

A Teacher’s Checklist for Evaluating Treatment Intrusiveness

Teachers are frequently involved in developing and evaluating treatments for problematic behaviors. Along with other members of the interdisciplinary team, they must determine the level of intrusiveness that a treatment may have on a student. Several factors that influence the intrusiveness of treatment procedures are described. These factors were used to develop a checklist that could be used systematically by teachers to evaluate the intrusiveness of treatments recommended by treatment teams. After the checklist was administered to a group of preservice teachers, it was found to be capable of discriminating among several treatment options described in a series of case vignettes. The implications of incorporating such a checklist into the design and implementation of treatments for problem behavior are discussed.Les enseignants sont souvent impliqués dans le développement et l’évaluation de traitements des problèmes de comportement. De concert avec d’autres membres d’une équipe interdisciplinaire, ils doivent déterminer dans quelle mesure un traitement est intrusif pour l’élève. L’article décrit plusieurs facteurs qui influencent le degré de discrétion des procédures. À partir de ces facteurs, on a dressé une liste de vérification dont pourraient se servir les enseignants de façon systématique pour évaluer à quel point les procédures recommandées par les équipes de traitement sont intrusives. La liste a été présentée à un groupe de stagiaires et s’est avérée capable de distinguer plusieurs options de traitement décrites dans une série de vignettes d’étude de cas. S’ensuit une discussion portant sur les conséquences d’incorporer une telle liste de vérification dans la conception et la mise en œuvre de traitements pour les problèmes de comportement

Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/117120/1/ecy2012935992.pd

Minute-of-Arc Resolution Gamma ray Imaging Experiment—MARGIE

MARGIE (Minute-of-Arc Resolution Gamma-ray Imaging Experiment) is a large area(∼104 cm2), wide field-of-view (∼1 sr), hard X-ray/gamma-ray (∼20–600 keV) coded-mask imaging telescope capable of performing a sensitive survey of both steady and transient cosmic sources. MARGIE has been selected for a NASA mission-concept study for an Ultra Long Duration (100 day) Balloon flight. We describe our program to develop the instrument based on new detector technology of either cadmium zinc telluride (CZT) semiconductors or pixellated cesium iodide (CsI) scintillators viewed by fast-timing bi-directional charge-coupled devices (CCDs). The primary scientific objectives are to image faint Gamma-Ray Bursts (GRBs) in near-real-time at the low intensity (high-redshift) end of the logN-logS distribution, thereby extending the sensitivity of present observations, and to perform a wide field survey of the Galactic plane

MARGIE: A gamma-ray burst ultra-long duration balloon mission

We are designing MARGIE as a 100 day ULDB mission to: a) detect and localize gamma-ray bursts; and b) survey the hard X-ray sky. MARGIE will consist of one small field-of-view (FOV) and four large FOV coded mask modules mounted on a balloon gondola. The burst position will be calculated onboard and disseminated in near-real time, while information about every count will be telemetered to the ground for further analysis. In a 100-day mission we will localize ∼40 bursts with peak photon fluxes from 0.14 to ∼5 ph cm−2 s−1 using 1 s integrations; the typical localization resolution will be better than ∼2 arcminutes

To Link or Not to Link? Multiple Team Membership and Unit Performance

Multiple team membership is common in today’s team-based organizations, but little is known about its relationship with collective effectiveness across teams. We adopted a microfoundations framework utilizing existing individual- and team-level research to develop a higher-level perspective on multiple team membership’s relationship with performance of entire units of teams. We tested our predictions with data collected from 849 primary care units of the Veterans Health Administration serving over 4.2 million patients. In this context, we found multiple team membership is negatively associated with unit performance, and this negative relationship is exacerbated by task complexity

Intrusiveness of behavioral treatments for children with autism and developmental disabilities: An initial investigation.

The behaviors frequently displayed by students with autism can place them at risk for overly reactive behavior interventions with unwanted side effects. The current study examined the level of intrusiveness of behavioral treatments developed for 198 students with disabilities from 13 different states. Results demonstrated that students diagnosed with autism had proportionally more intrusive behavior interventions when compared to students in five other disability categories and indicated that many students with autism were unnecessarily subjected to highly intrusive behavior interventions. The implications of these findings are discussed, and recommendations for future research are provided

The Use of a Book Club to Promote Biomedical Trainee Professional Development

Professional development for biomedical doctoral and postdoctoral trainees is vital, especially due to the increase in individuals pursuing non-faculty career paths. We created a professional development-focused discussion group between trainees and faculty/staff by utilizing a book club format in which monthly small group meetings occurred over an 8-month period. A pre- and post-survey consisting of Likert and free-response questions was completed by participants. Results demonstrated that after the book club, trainees: 1) were more knowledgeable about a variety of career paths; 2) had improved awareness of their interests in relation to their career; 3) were more knowledgeable of their transferrable skills; 4) were more comfortable engaging with their PI and completing/updating an Individual Development Plan; 5) were more likely to find mentors in addition to their PI to address career specific needs; and 6) were more likely to seek opportunities to conduct informational interviews or experiential learning. Additionally, we found that faculty/staff: 1) were more knowledgeable about careers outside of academia; 2) had greater consideration for their mentee\u27s values and interests in relation to their career; 3) had a better understanding of their mentee\u27s transferable skills; and 4) were more comfortable engaging with their mentee about their career path and addressing an Individual Development Plan. Overall, we found that the utilization of a book club consisting of trainees and faculty/staff as a professional development tool was beneficial for both groups of participants, and this format is feasible for use in biomedical education professional development

Intrusiveness of Behavioral Treatments for Children with Autism and Developmental Disabilities: An Initial Investigation

The behaviors frequently displayed by students with autism can place them at risk for overly reactive behavior interventions with unwanted side effects. The current study examined the level of intrusiveness of behavioral treatments developed for 198 students with disabilities from 13 different states. Results demonstrated that students diagnosed with autism had proportionally more intrusive behavior interventions when compared to students in five other disability categories and indicated that many students with autism were unnecessarily subjected to highly intrusive behavior interventions. The implications of these findings are discussed, and recommendations for future research are provided

THOSE WITH THE MOST FIND IT HARDEST TO SHARE: EXPLORING LEADER RESISTANCE TO THE IMPLEMENTATION OF TEAM-BASED EMPOWERMENT

We use a convergent parallel mixed methods approach to explore barriers to the successful implementation of a team-based empowerment initiative within the Veterans Health Administration. Although previous research has suggested that leaders often actively obstruct empowerment initiatives, little is known about the reasons behind and effects of such hindering. Using a longitudinal quasi-experimental design, we support a hypothesis that higher-status physician leaders are less successful than lower-status nonphysician leaders in implementing team-based empowerment. In parallel, we analyze qualitative data obtained through interviews conducted during early months of the teambased empowerment initiative to identify common themes for why and how leaders facilitated or obstructed implementation. Leader identity work and leader delegation were identified as themes explaining (1) why higher-status leaders struggled with the new empowering role and (2) how specific leader actions either facilitated or inhibited sharing of tasks and leadership. Results suggest that team-based empowerment creates a status threat for high-status leaders who then struggle to protect their old identity as someone with distinct professional capabilities, which in turn leads to improper delegation behavior. Therefore, in order for team-based empowerment to succeed, leaders may need to change their perceptions of who they are before they will change what they do