Dispensing Injustice: Stolt-Nielsen and Its Implications - Stolt-Nielsen S.A. v. AnimalFeeds Int\u27l Corp.

The immediate effect of the holding was to allow a group of corporate defendants to use their superior bargaining position in the contracting process to effectively shield themselves from liability. Although Stolt-Nielsen involved business entities, the case also has implications in the consumer context. If the Court were to extend the reasoning of the case to disputes involving adhesion contracts, corporations would enjoy this immunity in the context of consumer disputes. Far from a hypothetical exercise in the reaches of Supreme Court jurisprudence, the Court is expected to decide this very issue during the 2010 term. In light of these concerns, Congress should enact the Arbitration Fairness Act in order to prevent further injustice

Non-canonical functions of the RB protein in cancer

The canonical model of RB-mediated tumour suppression developed over the past 30 years is based on the regulation of E2F transcription factors to restrict cell cycle progression. Several additional functions have been proposed for RB, on the basis of which a non-canonical RB pathway can be described. Mechanistically, the non-canonical RB pathway promotes histone modification and regulates chromosome structure in a manner distinct from cell cycle regulation. These functions have implications for chemotherapy response and resistance to targeted anticancer agents. This Opinion offers a framework to guide future studies of RB in basic and clinical research

Closing the brief case: A Fatal Case of Necrotizing Fasciitis Due to Multidrug-Resistant Acinetobacter baumannii

ANSWERS TO SELF-ASSESSMENT QUESTIONS 1. What is the most common etiology of monomicrobial (type 2) necrotizing fasciitis? a. Acinetobacter baumannii b. Staphylococcus aureus c. Streptococcus pyogenes d. Vibrio vulnificus Answer: c. Although all of the organisms listed cause type 2 necrotizing fasciitis, the most common cause is still S. pyogenes, with an incidence of 0.4 per 100,000 in the United States. Due to variations in reporting practices, the exact incidences of other etiologies are not known, but they are less common than S. pyogenes

Effects of Maraviroc and Efavirenz on Markers of Immune Activation and Inflammation and Associations with CD4+ Cell Rises in HIV-Infected Patients

Maraviroc treatment for HIV-1 infected patients results in larger CD4(+) T cell rises than are attributable to its antiviral activity alone. We investigated whether this is due to modulation of T cell activation and inflammation.Thirty maraviroc-treated patients from the Maraviroc versus Efavirenz Regimens as Initial Therapy (MERIT) study were randomly selected from among those who had CCR5-tropic (R5) HIV on screening and achieved undetectable HIV RNA (<50 copies/mL) by Week 48. Efavirenz-treated controls were matched for baseline characteristics to the maraviroc-treated patients selected for this substudy. Changes in immune activation and inflammation markers were examined for associations with CD4(+) T cell changes. Maraviroc treatment tended to result in more rapid decreases in CD38 expression on CD4(+) T cells and in plasma D-dimer concentrations than did treatment with efavirenz. The proportion of patients with high-sensitivity C-reactive protein >2 µg/mL increased from 45% to 66% in the efavirenz arm, but remained constant in the maraviroc arm (P = 0.033). Decreases in CD38 expression on CD8(+) T cells were correlated with CD4(+) T cell rises for maraviroc treatment (r = -0.4, P = 0.048), but not for treatment with efavirenz.Maraviroc-treated patients had earlier, modest decreases in certain markers of immune activation and inflammation, although in this small study, many of the differences were not statistically significant. Levels of high-sensitivity C-reactive protein remained constant in the maraviroc arm and increased in the efavirenz arm. Decreases in immune activation correlated with increased CD4(+) T cell gains.ClinicalTrials.gov NCT00098293

Cluster randomized adaptive implementation trial comparing a standard versus enhanced implementation intervention to improve uptake of an effective re-engagement program for patients with serious mental illness

Abstract Background Persons with serious mental illness (SMI) are disproportionately burdened by premature mortality. This disparity is exacerbated by poor continuity of care with the health system. The Veterans Health Administration (VA) developed Re-Engage, an effective population-based outreach program to identify veterans with SMI lost to care and to reconnect them with VA services. However, such programs often encounter barriers getting implemented into routine care. Adaptive designs are needed when the implementation intervention requires augmentation within sites that do not initially respond to an initial implementation intervention. This protocol describes the methods used in an adaptive implementation design study that aims to compare the effectiveness of a standard implementation strategy (Replicating Effective Programs, or REP) with REP enhanced with External Facilitation (enhanced REP) to promote the uptake of Re-Engage. Methods/Design This study employs a four-phase, two-arm, longitudinal, clustered randomized trial design. VA sites (n = 158) across the United States with a designated Re-Engage provider, at least one Veteran with SMI lost to care, and who received standard REP during a six-month run-in phase. Subsequently, 88 sites with inadequate uptake were stratified at the cluster level by geographic region (n = 4) and VA regional service network (n = 20) and randomized to REP (n = 49) vs. enhanced REP (n = 39) in phase two. The primary outcome was the percentage of veterans on each facility outreach list documented on an electronic web registry. The intervention was at the site and network level and consisted of standard REP versus REP enhanced by external phone facilitation consults. At 12 months, enhanced REP sites returned to standard REP and 36 sites with inadequate participation received enhanced REP for six months in phase three. Secondary implementation outcomes included the percentage of veterans contacted directly by site providers and the percentage re-engaged in VA health services. Discussion Adaptive implementation designs consisting of a sequence of decision rules that are tailored based on a site’s uptake of an effective program may produce more relevant, rapid, and generalizable results by more quickly validating or rejecting new implementation strategies, thus enhancing the efficiency and sustainability of implementation research and potentially leading to the rollout of more cost-efficient implementation strategies. Trial registration Current Controlled Trials ISRCTN21059161 .http://deepblue.lib.umich.edu/bitstream/2027.42/112609/1/13012_2013_Article_711.pd

Cluster randomized trial comparing standard versus enhanced implementation strategies for improving outreach to persons with SMI: 12-month results

http://deepblue.lib.umich.edu/bitstream/2027.42/134545/1/13012_2015_Article_940.pd

Estimating Amur tiger (\u3ci\u3ePanthera tigris altaica\u3c/i\u3e) kill rates and potential consumption rates using global positioning system collars

The International Union for Conservation of Nature has classified all subspecies of tigers (Panthera tigris) as endangered and prey depletion is recognized as a primary driver of declines. Prey depletion may be particularly important for Amur tigers (P. t. altaica) in the Russian Far East, living at the northern limits of their range and with the lowest prey densities of any tiger population. Unfortunately, rigorous investigations of annual prey requirements for any tiger population are lacking. We deployed global positioning system (GPS) collars on Amur tigers during 2009–2012 to study annual kill rates in the Russian Far East. We investigated 380 GPS location clusters and detected 111 kill sites. We then used logistic regression to model both the probability of a kill site at location clusters and the size of prey species at kill sites according to several spatial and temporal cluster covariates. Our top model for predicting kill sites included the duration of the cluster in hours and cluster fidelity components as covariates (overall classification success 86.3%; receiver operating characteristic score of 0.894). Application of the model to all tiger GPS data revealed that Amur tigers in this study made a kill once every 6.5 days (95% confidence interval [95% CI] 5.9–7.2 days) and consumed an estimated average of 8.9 kg of prey biomass per day (95% CI 8.8–9.0 kg/day). The success of efforts to reverse tiger declines will be at least partially determined by wildlife managers’ ability to conserve large ungulates at adequate densities for recovering tiger populations

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

Taking Healthy Steps: rationale, design and baseline characteristics of a randomized trial of a pedometer-based internet-mediated walking program in veterans with chronic obstructive pulmonary disease

Abstract Background Low levels of physical activity are common in patients with chronic obstructive pulmonary disease (COPD), and a sedentary lifestyle is associated with poor outcomes including increased mortality, frequent hospitalizations, and poor health-related quality of life. Internet-mediated physical activity interventions may increase physical activity and improve health outcomes in persons with COPD. Methods/Design This manuscript describes the design and rationale of a randomized controlled trial that tests the effectiveness of Taking Healthy Steps, an Internet-mediated walking program for Veterans with COPD. Taking Healthy Steps includes an uploading pedometer, a website, and an online community. Eligible and consented patients wear a pedometer to obtain one week of baseline data and then are randomized on a 2:1 ratio to Taking Healthy Steps or to a wait list control. The intervention arm receives iterative step-count feedback; individualized step-count goals, motivational and informational messages, and access to an online community. Wait list controls are notified that they are enrolled, but that their intervention will start in one year; however, they keep the pedometer and have access to a static webpage. Discussion Participants include 239 Veterans (mean age 66.7 years, 93.7% male) with 155 randomized to Taking Healthy Steps and 84 to the wait list control arm; rural-living (45.2%); ever-smokers (93.3%); and current smokers (25.1%). Baseline mean St. George’s Respiratory Questionnaire Total Score was 46.0; 30.5% reported severe dyspnea; and the average number of comorbid conditions was 4.9. Mean baseline daily step counts was 3497 (+/- 2220). Veterans with COPD can be recruited to participate in an online walking program. We successfully recruited a cohort of older Veterans with a significant level of disability including Veterans who live in rural areas using a remote national recruitment strategy. Trial registration Clinical Trials.gov NCT01102777http://deepblue.lib.umich.edu/bitstream/2027.42/109506/1/12890_2014_Article_479.pd