All the World Wide Web is a Stage: Free Speech, Expressive Association, and the Right to Choose Your Audience

To determine whether punishing the disclosure of illegally obtained information violates the First Amendment’s guarantee of freedom of speech, the Supreme Court currently applies a public concern test. Previously, the primary example of this conflict was the use of state or federal wiretapping statutes to punish television journalists broadcasting wire-tapped conversations. Today, the same statutes may punish individuals distributing similar recordings on the Internet. Because of the increasing importance of online communication and the increasing concern about off-line conduct being posted online, an appropriate First Amendment framework must balance the rights of the public to obtain information, the rights of the media to disclose information, and the rights of speakers to determine their audience. The public concern test fails in this endeavor. Instead, courts should balance the right to disclose the recording against the recorded speaker’s right to freedom of association. This approach rejects a dichotomy between public and private as ill-suited to online communication and instead focuses on protecting the rights of speakers to choose their audience. Grounded in the First Amendment’s protection of expressive association and anonymous speech, this Note proposes that the need to protect unpopular or minority viewpoints from unwanted online publicity justifies limits on the dissemination of certain types of recordings

UNH Digital Adventures 2020

A compilation of virtual activities to help educators engage their students in the online learning environment

Modeling of the Influence of Sea Ice Cycle and Langmuir Circulation on the Upper Ocean Mixed Layer Depth and Freshwater Distribution at the West Antarctic Peninsula.

The Southern Ocean is chronically undersampled due to its remoteness, harsh environment, and sea ice cover. Ocean circulation models yield significant insight into key processes and to some extent obviate the dearth of data; however, they often underestimate surface mixed layer depth (MLD), with consequences for surface water-column temperature, salinity, and nutrient concentration. In this study, a coupled circulation and sea ice model was implemented for the region adjacent to the West Antarctic Peninsula, a climatically sensitive region which has exhibited decadal trends towards higher ocean temperature, shorter sea ice season, and increasing glacial freshwater input, overlain by strong interannual variability. Hindcast simulations were conducted with different air-ice drag coefficients and Langmuir circulation parameterizations to determine the impact of these factors on MLD. Including Langmuir circulation deepened the surface mixed layer, with the deepening being more pronounced in the shelf and slope regions. Optimal selection of an air-ice drag coefficient also increased modeled MLD by similar amounts and had a larger impact in improving the reliability of the simulated MLD interannual variability. This study highlights the importance of sea ice volume and redistribution to correctly reproduce the physics of the underlying ocean, and the potential of appropriately parameterizing Langmuir circulation to help correct for biases towards shallow MLD in the Southern Ocean. The model also reproduces observed freshwater patterns in the West Antarctic Peninsula during late summer and suggests that areas of intense summertime sea ice melt can still show net annual freezing due to high sea ice formation during the winter

Sources, variability and fate of freshwater in the Bellingshausen Sea, AntarcticaSources, variability and fate of freshwater in the Bellingshausen Sea, Antarctica

During the second half of the twentieth century, the Antarctic Peninsula was subjected to a rapid increase in air temperatures. This was accompanied by a reduction in sea ice extent, increased precipitation and a dramatic retreat of glaciers associated with an increase in heat flux from deep ocean water masses. Isotopic tracers have been used previously to investigate the relative importance of the different freshwater sources to the adjacent Bellingshausen Sea (BS), but the data coverage is strongly biased toward summer. Here we use a regional model to investigate the ocean's response to the observed changes in its different freshwater inputs (sea ice melt/freeze, precipitation, evaporation, iceberg/glacier melt, and ice shelf melt). The model successfully recreates BS water masses and performs well against available freshwater data. By tracing the sources and pathways of the individual components of the freshwater budget, we find that sea ice dominates seasonal changes in the total freshwater content and flux, but all sources make a comparable contribution to the annual-mean. Interannual variability is dominated by sea ice and precipitation. Decadal trends in the salinity and stratification of the ocean are investigated, and a 20-year surface freshening from 1992-2011 is found to be predominantly driven by decreasing autumn sea ice growth. These findings will help to elucidate the role of freshwater in driving circulation and water column structure changes in this climatically-sensitive region

Independent Validation of EarlyR Gene Signature in BIG 1-98: A Randomized, Double-Blind, Phase III Trial Comparing Letrozole and Tamoxifen as Adjuvant Endocrine Therapy for Postmenopausal Women with Hormone Receptor-Positive, Early Breast Cancer

Background EarlyR gene signature in estrogen receptor–positive (ER+) breast cancer is computed from the expression values of ESPL1, SPAG5, MKI67, PLK1, and PGR. EarlyR has been validated in multiple cohorts profiled using microarrays. This study sought to verify the prognostic features of EarlyR in a case-cohort sample from BIG 1–98, a randomized clinical trial of ER+ postmenopausal breast cancer patients treated with adjuvant endocrine therapy (letrozole or tamoxifen). Methods Expression of EarlyR gene signature was estimated by Illumina cDNA-mediated Annealing, Selection, and Ligation assay of RNA from formalin-fixed, paraffin-embedded primary breast cancer tissues in a case-cohort subset of ER+ women (N = 1174; 216 cases of recurrence within 8 years) from BIG 1–98. EarlyR score and prespecified risk strata (≤25 = low, 26–75 = intermediate, >75 = high) were “blindly” computed. Analysis endpoints included distant recurrence–free interval and breast cancer–free interval at 8 years after randomization. Hazard ratios (HRs) and test statistics were estimated with weighted analysis methods. Results The distribution of the EarlyR risk groups was 67% low, 19% intermediate, and 14% high risk in this ER+ cohort. EarlyR was prognostic for distant recurrence–free interval; EarlyR high-risk patients had statistically increased risk of distant recurrence within 8 years (HR = 1.73, 95% confidence interval = 1.14 to 2.64) compared with EarlyR low-risk patients. EarlyR was also prognostic of breast cancer–free interval (HR = 1.74, 95% confidence interval = 1.21 to 2.62). Conclusions This study confirmed the prognostic significance of EarlyR using RNA from formalin-fixed, paraffin-embedded tissues from a case-cohort sample of BIG 1–98. EarlyR identifies a set of high-risk patients with relatively poor prognosis who may be considered for additional treatment. Further studies will focus on analyzing the predictive value of EarlyR signature

The IBER study: a feasibility randomised controlled trial of imagery based emotion regulation for the treatment of anxiety in bipolar disorder

BACKGROUND: Intrusive mental imagery is associated with anxiety and mood instability within bipolar disorder and therefore represents a novel treatment target. Imagery Based Emotion Regulation (IBER) is a brief structured psychological intervention developed to enable people to use the skills required to regulate the emotional impact of these images. METHODS: Participants aged 18 and over with a diagnosis of bipolar disorder and at least a mild level of anxiety were randomly assigned (1:1) to receive IBER plus treatment as usual (IBER + TAU) or treatment as usual alone (TAU). IBER was delivered in up to 12 sessions overs 16 weeks. Clinical and health economic data were collected at baseline, end of treatment and 16-weeks follow-up. Objectives were to inform the recruitment process, timeline and sample size estimate for a definitive trial and to refine trial procedures. We also explored the impact on participant outcomes of anxiety, depression, mania, and mood stability at 16-weeks and 32-weeks follow-up. RESULTS: Fifty-seven (28: IBER + TAU, 27: TAU) participants from two sites were randomised, with 50 being recruited within the first 12 months. Forty-seven (82%) participants provided outcome data at 16 and 32-weeks follow-up. Thirty-five participants engaged in daily mood monitoring at the 32-week follow-up stage. Retention in IBER treatment was high with 27 (96%) attending ≥ 7 sessions. No study participants experienced a serious adverse event. DISCUSSION: The feasibility criteria of recruitment, outcome completion, and intervention retention were broadly achieved, indicating that imagery-focused interventions for bipolar disorder are worthy of further investigation

Genotyping concordance in DNA extracted from formalin‐fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135708/1/mol22015991868.pd

Digital Quantification of Gene Expression in Sequential Breast Cancer Biopsies Reveals Activation of an Immune Response

Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. A useful approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy and the definitive surgery. These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define the biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention using the Nanostring nCounter platform. We found that while the majority of the transcripts did not vary between the two biopsies, there was evidence of activation of immune related genes in response to the first biopsy and further investigations of the immune changes after a biopsy in early breast cancer seem warranted

Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX

Introduction: The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown. Methods: We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections. Results: ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared. Conclusions: Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression. Trial registration Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX)