What Price Innocence - A Realistic View of the Innocent Landowner Defense under CERCLA.

Congress enacted the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) to provide the federal government and the states with authority to clean up hazardous waste sites. This article discusses the significance of the so-called “innocent landowner defense” under CERCLA. This Act imposed liability on landowners regardless of the landowner’s contribution to, or awareness of, the presence of hazardous substances on their acquired property. The exceedingly, and apparently unintentionally, harsh impact of CERCLA liability soon became apparent. This article addresses a brief summary of the statute and the manner in which the innocent landowner defense came into existence. It also details recent efforts to clarify the availability of the defense and to analyze the effect, if any, such efforts had on the amorphous innocent landowner defense. Landowner innocence under CERCLA is an elusive concept. The original CERCLA statute did not contemplate a defense of innocence for landowners. This rendered them strictly liable for cleanup liability with only the narrowest of limited defenses available. The Superfund Amendments and Reauthorization Act of 1986 (SARA), purported to provide a defense to “innocent” landowners. However, it failed to define the parameters needed to prove innocence. Proposed legislation amending SARA’s innocent landowner provision appears to do little more than to assimilate the current practices employed by landowners hoping to meet the “all appropriate inquiry” standard. Then, it only proffers them as a “rebuttable presumption” the inquiries have been met. The EPA’s subsequent Guidance Document appears to take an even different tack by implying perhaps that innocence may not be suitable for definition at all, but that it will be won or lost on a case-by-case basis

Translating Research Into Practice: Speeding the Adoption of Innovative Health Care Programs

Looks at case studies of four innovative clinical programs to determine key factors influencing the diffusion and adoption of innovations in health care

Measuring functional brain recovery in regenerating planarians by assessing the behavioral response to the cholinergic compound cytisine

Planarians are traditional model invertebrates in regeneration and developmental biology research that also display a variety of quantifiable behaviors useful to screen for pharmacologically active compounds. One such behavior is the expression of seizure-like movements (pSLMs) induced by a variety of substances. Previous work from our laboratory showed that cocaine, but not nicotine, induced pSLMs in intact but not decapitated planarians. Interestingly, as decapitated planarians regenerated their heads, they gradually recovered their sensitivity to cocaine. These results suggested a method to assess planarian brain regeneration and a possible way of identifying compounds that could enhance or hold back brain regeneration. In the present work, we demonstrate that the cholinergic agent cytisine is a suitable reference compound to apply our method. Cytisine induces pSLMs in a concentration-dependent manner in intact (but not decapitated) planarians of the species Girardia tigrina. Based on our data, we developed a behavioral protocol to assess planarian brain regeneration over time. We tested this method to measure the effect of ethanol on G. tigrina’s brain regeneration. We found that ethanol slows down the rate of planarian brain regeneration in a concentration-dependent manner, consistently with data from other research groups that tested ethanol effects on planarian brain regeneration using different behavioral protocols. Thus, here we establish a general method using cytisine-induced pSLMs as an indicator of brain regeneration in planarians, a method that shows potential for assessing the effect of pharmacologically active compounds in this process

Cotinine antagonizes the behavioral effects of nicotine exposure in the planarian Girardia tigrina

Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine’s beneficial effects and few of its undesirable ones. It is not known whether cotinine is a product of nicotine metabolism in planarians. We found that cotinine by itself does not seem to elicit any behavioral effects in planarians up to a concentration of 1 mM. We also show that cotinine antagonizes the aforementioned nicotine-induced motility decrease and also decreases the expression of nicotine-induced pSLMs in a concentration-dependent manner. Also cotinine prevents the manifestation of some of the withdrawal-like behaviors induced by nicotine in our experimental organism. Thus, we obtained evidence supporting that cotinine antagonizes nicotine in this planarian species. Possible explanations include competitive binding of both compounds at overlapping binding sites, at different nicotinic receptor subtypes, or maybe allosteric interactions

Game, Set, Match: Conquer Your Library’s Content Management Needs with LibGuides CMS

With the ability to create uniquely branded groups of guides limited to specific content creators and audiences, LibGuides CMS significantly expands the flexibility of the LibGuides platform to support libraries’ content management needs. During this session, presenters will share a series of use cases with LibGuides CMS, including two limited-access staff intranet sites; two limited-permission student-curated course sites; a uniquely branded special collections event site; a uniquely-branded peer-reviewed literary journal; and two faculty-curated conference presentation sites. This session will be of interest to anyone using LibGuides, LibGuides CMS, or similar content management systems

Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice

Objective: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is freqnency-dependent, as might be expected if attributable to changes in SR Ca²⁺ loading. Methods: Intracellular [Ca²⁺] and contractile force were measured at room temperature (22 °C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n=6) or SERCA2a transgenic (n=6) mice. Results: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca²⁺ transients (transgenics: 1.56 ± 0.09 μmol/l, controls: 1.21 ± 0.14) and twitches (transgenics: 21.71 ± 0.91 mN/mm², controls: 13.74 ± 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). Conclusion: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Development of a Certificate in Healthcare Improvement for Inter-Professional Teams

Introduction To address gaps in care team improvement-science education and connect geographically dispersed learners, we created a healthcare improvement certificate program, now completing the third program year, for inter-professional (IP) healthcare teams, including third year medical students. Methods This hybrid learning program consists of five modules: Learning Healthcare Systems, Improvement Science, Patient Safety and Diagnostic Error, Population Health and Health Equity and Leading Change. The curricular materials are comprised of focused readings, concise videos, faculty-moderated discussion boards, weekly synchronous calls of participants with faculty, and a longitudinal improvement project. The faculty are content experts, and worked with a curricular designer to define learning objectives and develop content. Results We have completed three years of this six-month program, training 61 participants (17 of whom were medical students) at 14 sites. In the third year, several medical students participated without an IP team. Development of the materials has been iterative, with feedback from learners and faculty used to shape the materials. Discussion We demonstrate the development and rollout of a hybrid-learning program for diverse and geographically dispersed IP teams, including medical students. Time restrictions limited the depth of topics, and scheduling overlap caused some participants to miss the interactive calls. We plan to evaluate the utility of the program for participants over time, using qualitative methods. Conclusion This educational model is feasible for IP teams studying improvement science and implementing change projects, and can be adopted to dispersed geographic settings

Climate change concerns impact on young Australians’ psychological distress and outlook for the future

Aims: Climate change is escalating and will disproportionately affect young people. Research on the mental health consequences of worry or concerns related to climate change are so far limited. This study aims to evaluate the extent of climate change concern in young people aged 15–19, its association with various demographic factors and its impact on psychological distress and future outlook. Understanding the impact of climate concerns on young people's mental wellbeing is crucial for identifying effective measures and building resilience. Methods: Climate concerns, psychological distress, and future outlook were measured in the 2022 Mission Australia Youth Survey, Australia's largest annual population-wide survey of young people aged 15 to 19 (N = 18,800). Multinomial logistic regression models were used to map factors associated with climate concerns and assess whether climate concerns are associated with psychological distress and future outlook. Results: One in four young people reported feeling very or extremely concerned about climate change. Climate concerns were higher among individuals identifying as female or gender diverse, or who self-reported a mental health condition. After controlling for confounding factors, we found those who were very or extremely concerned about climate change to be more likely to have high psychological distress than those not at all concerned (Relative risk ratio (RRR) = 1.81; 95% CI: 1.56–2.11), and more likely to have a negative future outlook (RRR = 1.52; 95% CI: 1.27–1.81). These associations were stronger among participants who reported to be gender diverse, Indigenous or from outer-regional/remote areas. Conclusion: This study identified associations between climate concerns, psychological distress, and future outlook among young people. Immediate attention from research and policy sectors to support climate change education, communication strategies and targeted interventions is urgently required to mitigate long-term impacts on young people's wellbeing.</p

Inhibition of HER2 enriches for Jagged1-dependent breast cancer stem cells: role for membrane Jagged1

Purpose: Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer is driven by cells possessing stem-like properties of self-renewal and differentiation, referred to as Cancer Stem Cells (CSCs). CSCs are implicated in radiotherapy, chemotherapy resistance, and tumor recurrence. Notch promotes breast CSCs survival and self-renewal, and overexpression of Notch1 and the Notch ligand Jagged1 predict poor outcome. Resistance to anti-HER2 therapy in HER2+ breast cancer requires Notch1, and that combination of trastuzumab and a Gamma Secretase Inhibitor (GSI) prevents tumor relapse in xenograft models. Experimental Design: The current study investigates mechanisms by which HER2 tyrosine kinase activity regulates Notch-dependent CSC survival and tumor initiation. Results: Lapatinib-mediated HER2 inhibition shifts the population of HER2+ breast cancer cells from low membrane Jagged1 expressing to higher levels, independent of sensitivity to anti-HER2 treatment within the bulk cell population. This increase in membrane Jagged1 is associated with higher Notch receptor expression, activation, and enrichment of CSCs in vitro and in vivo. Importantly, lapatinib treatment results in growth arrest and cell death of Jagged1 low-expressing cells while the Jagged1 high-expressing cells continue to cycle. High membrane Jagged1 protein expression predicts poor overall cumulative survival in women with HER2+ breast cancer. Conclusions: These results indicate that higher membrane Jagged1 expression may be used to either predict response to anti-HER2 therapy or for detection of Notch sensitive CSCs post therapy. Sequential blockade of HER2 followed by Jagged1 or Notch could be more effective than simultaneous blockade to prevent drug resistance and tumor progression