Systematic assessment of HER2/neu in gynecologic neoplasms, an institutional experience.

BackgroundHER2/neu overexpression and/or amplification has been widely studied in a number of solid tumors, primarily in the breast. In gynecologic neoplasms, determination of HER2/neu status has not been well studied as a predictive biomarker in anti-HER2/neu treatment.MethodsWe systematically evaluated the HER2/neu reactions by immunohistochemistry and fluorescent in situ hybridization in malignant gynecologic neoplasms as experienced in our institution.ResultsThe HER2/neu overexpression or amplification occurred in 8 % of the cancers of the gynecological organs in our series. Majority of the HER2/neu overexpression and/or amplification occurred in clear cell (27 %) and serous (11 %) carcinomas. HER2/neu positivity was also seen in undifferentiated as well as in mixed clear cell and serous carcinomas. Discordant IHC and FISH results (positive by FISH but not IHC) was seen in 2 cases. Majority of the HER2/neu overexpression and/or amplification occurs in the endometrium rather than the ovary. Heterogeneity of the HER2/neu by IHC staining was in < 2 % of the tumors in our series.ConclusionsWe recommend the HER2/neu studies on Müllerian carcinomas of clear cell, serous, and undifferentiated types, particularly when they arise in the endometrium. Since there are some discordant IHC/FISH results, we also propose performing the HER2/neu testing by FISH when the IHC score is less than 3 + 

Behavioral Deficits and Axonal Injury Persistence after Rotational Head Injury Are Direction Dependent

Pigs continue to grow in importance as a tool in neuroscience. However, behavioral tests that have been validated in the rodent model do not translate well to pigs because of their very different responses to behavioral stimuli. We refined metrics for assessing porcine open field behavior to detect a wide spectrum of clinically relevant behaviors in the piglet post-traumatic brain injury (TBI). Female neonatal piglets underwent a rapid non-impact head rotation in the sagittal plane (n=8 evaluable) or were instrumented shams (n=7 evaluable). Open field testing was conducted 1 day prior to injury (day −1) in order to establish an individual baseline for analysis, and at days +1 and +4 after injury. Animals were then killed on day +6 after injury for neuropathological assessment of axonal injury. Injured piglets were less interested in interacting with environmental stimuli and had a lower activity level than did shams. These data were compared with previously published data for axial rotational injuries in neonatal piglets. Acute behavioral outcomes post-TBI showed a dependence on the rotational plane of the brain injury, with animals with sagittal injuries demonstrating a greater level of inactivity and less random usage of the open field space than those with axial injuries. The persistence of axonal injury is also dependent on the rotational plane, with sagittal rotations causing more prolonged injuries than axial rotations. These results are consistent with animal studies, finite element models, and studies of concussions in football, which have all demonstrated differences in injury severity depending upon the direction of head impact rotation

Afatinib use in recurrent epithelial ovarian carcinoma.

•Genomic tumor testing is an important tool in guiding treatment for gynecologic malignancies.•Targetable mutations may lead to new therapies in gynecologic cancer treatment.•Her2/neu mutations in serous ovarian carcinomas can be targeted with ERBB2 inhibitors.•Afatinib shows promising response rates in lung cancers carrying Her2/neu mutations.•Afatinib may be effective in serous ovarian tumors exhibiting Her2/neu or ERBB2 mutations

Targeting the Ets Binding Site of the HER2/neu Promoter with Pyrrole-Imidazole Polyamides

Three DNA binding polyamides (1-3) were synthesized that bind with high affinity (Ka = 8.7·10^9 M^-1 to 1.4·10^10 M^-1) to two 7-base pair sequences overlapping the Ets DNA binding site (EBS; GAGGAA) within the regulatory region of the HER2/neu proximal promoter. As measured by electrophoretic mobility shift assay, polyamides binding to flanking elements upstream (1) or downstream (2 and 3) of the EBS were one to two orders of magnitude more effective than the natural product distamycin at inhibiting formation of complexes between the purified EBS protein, epithelial restricted with serine box (ESX), and the HER2/neu promoter probe. One polyamide, 2, completely blocked Ets-DNA complex formation at 10 nM ligand concentration, whereas formation of activator protein-2-DNA complexes was unaffected at the activator protein-2 binding site immediately upstream of the HER2/neu EBS, even at 100 nM ligand concentration. At equilibrium, polyamide 1 was equally effective at inhibiting Ets/DNA binding when added before or after in vitro formation of protein-promoter complexes, demonstrating its utility to disrupt endogenous Ets-mediated HER2/neu preinitiation complexes. Polyamide 2, the most potent inhibitor of Ets-DNA complex formation by electrophoretic mobility shift assay, was also the most effective inhibitor of HER2/neu promoter-driven transcription measured in a cell-free system using nuclear extract from an ESX- and HER2/neu-overexpressing human breast cancer cell line, SKBR-3

First-order regret bounds for combinatorial semi-bandits

We consider the problem of online combinatorial optimization under semi-bandit feedback, where a learner has to repeatedly pick actions from a combinatorial decision set in order to minimize the total losses associated with its decisions. After making each decision, the learner observes the losses associated with its action, but not other losses. For this problem, there are several learning algorithms that guarantee that the learner's expected regret grows as $\widetilde{O}(\sqrt{T})$ with the number of rounds $T$. In this paper, we propose an algorithm that improves this scaling to $\widetilde{O}(\sqrt{{L_T^*}})$, where $L_T^*$ is the total loss of the best action. Our algorithm is among the first to achieve such guarantees in a partial-feedback scheme, and the first one to do so in a combinatorial setting.Comment: To appear at COLT 201

Explore no more: Improved high-probability regret bounds for non-stochastic bandits

This work addresses the problem of regret minimization in non-stochastic multi-armed bandit problems, focusing on performance guarantees that hold with high probability. Such results are rather scarce in the literature since proving them requires a large deal of technical effort and significant modifications to the standard, more intuitive algorithms that come only with guarantees that hold on expectation. One of these modifications is forcing the learner to sample arms from the uniform distribution at least $\Omega(\sqrt{T})$ times over $T$ rounds, which can adversely affect performance if many of the arms are suboptimal. While it is widely conjectured that this property is essential for proving high-probability regret bounds, we show in this paper that it is possible to achieve such strong results without this undesirable exploration component. Our result relies on a simple and intuitive loss-estimation strategy called Implicit eXploration (IX) that allows a remarkably clean analysis. To demonstrate the flexibility of our technique, we derive several improved high-probability bounds for various extensions of the standard multi-armed bandit framework. Finally, we conduct a simple experiment that illustrates the robustness of our implicit exploration technique.Comment: To appear at NIPS 201

NEU screen shows high accuracy in detecting cognitive impairment in older persons living with HIV

The NEUrocognitive (NEU) Screen is a practical tool proposed to screen for HIV-associated cognitive impairment in the clinical setting. This is a pencil-and-paper method that can be applied rapidly (<=10 minutes for administration) and has no copyright limitations. In this study, we aimed at investigating its diagnostic accuracy in an older population of persons living with HIV (PLWH), with cutoffs set at 30, 40, 50, and 60 years. Data were collected from a sample of 368 PLWH who underwent a comprehensive neuropsychological tests battery (gold standard). Results of statistical tests showed that accuracy of the NEU Screen increased with age of the participants. The highest degree of precision, with a sensitivity of 91% and specificity of 92%, was obtained for people ages 60 years or older (correct classification: 91%). These optimal results point to the great potential of the NEU Screen as a tool for detecting cognitive disorders in older PLWH

An Astronomical Account: A History of Hatter Planetarium from 1966-2006

When most individuals stare up at the vast dome of Hatter Planetarium, they often gaze upon the projected stars appearing on its surface, listening to an astronomical story told by one of its operators. However, there is a second story told by the planetarium itself. This story is the history of Hatter Planetarium, which spans five decades and includes the events in the lives of several individuals who have played a critical role in its existence at Gettysburg College. Its history has encompassed several phases of Gettysburg College traditions but is in danger of passing permanently and fixedly into the history books. Gettysburg College’s Hatter Planetarium is an example of a facility, rich in history, which has come to represent a steadfast bond between community and campus relations. [excerpt] Course Information: Course Title: HIST 300: Historical Method Academic Term: Spring 2006 Course Instructor: Dr. Michael J. Birkner \u2772 Hidden in Plain Sight is a collection of student papers on objects that are hidden in plain sight around the Gettysburg College campus. Topics range from the Glatfelter Hall gargoyles to the statue of Eisenhower and from historical markers to athletic accomplishments. You can download the paper in pdf format and click View Photo to see the image in greater detail.https://cupola.gettysburg.edu/hiddenpapers/1021/thumbnail.jp