Identifying the Burdens and Opportunities for Tribes and Communities in Federal Facility Cleanup Activities: Environmental Remediation Technology Assessment Matrix For Tribal and Community Decision-Makers

The cleanup of this country's federal facilities can affect a wide range of tribal and community interests and concerns. The technologies now in use, or being proposed by the Department of Energy, Department of Defense and other federal agencies can affect tribal treaty protected fishing, hunting and other rights, affect air and water quality thereby requiring the tribe to bear the burden of increased environmental regulation. The International Institute for Indigenous Resource Management developed a tribal and community decision-maker's Environmental Remediation Technology Assessment Matrix that will permit tribes and communities to array technical information about environmental remediation technologies against a backdrop of tribal and community environmental, health and safety, cultural, religious, treaty and other concerns and interests. Ultimately, the matrix will allow tribes and communities to assess the impact of proposed technologies on the wide range of tribal and community interests and will promote more informed participation in federal facility cleanup activities

Identifying the Burdens and Opportunities for Tribes and Communities in Federal Facility Cleanup Activities: Environmental Remediation Technology Assessment Matrix For Tribal and Community Decision-Makers

The cleanup of this country’s federal facilities can affect a wide range of tribal and community interests and concerns. The technologies now in use, or being proposed by the Department of Energy, Department of Defense and other federal agencies can affect tribal treaty protected fishing, hunting and other rights, affect air and water quality thereby requiring the tribe to bear the burden of increased environmental regulation. The International Institute for Indigenous Resource Management developed a tribal and community decision-maker’s Environmental Remediation Technology Assessment Matrix that will permit tribes and communities to array technical information about environmental remediation technologies against a backdrop of tribal and community environmental, health and safety, cultural, religious, treaty and other concerns and interests. Ultimately, the matrix will allow tribes and communities to assess the impact of proposed technologies on the wide range of tribal and community interests and will promote more informed participation in federal facility cleanup activities. This research was completed money allocated during Round 1 of the Citizens’ Monitoring and Technical Assessment Fund (MTA Fund). Clark University was named conservator of these works. If you have any questions or concerns please contact us at [email protected]://commons.clarku.edu/iiirm/1000/thumbnail.jp

Intended and unintended outcomes after FDA pediatric antidepressant warnings: a systematic review

Since 2003, the Food and Drug Administration (FDA) has warned that antidepressants may be associated with suicidal thoughts and behaviors among youth. An FDA advisory in 2003 and a black-box warning in 2005 focused on children and adolescents younger than age eighteen. The FDA expanded the black-box warning in 2007 to include young adults. Both warnings were intended to increase physician monitoring of suicidal thoughts and behaviors. Our systematic review identified thirty-four studies of depression and suicide-related outcomes after these warnings; eleven of these studies met research design criteria established to reduce biases. The eleven studies examined monitoring for suicidal thoughts and behaviors, physician visits for depression, depression diagnoses, psychotherapy visits, antidepressant treatment and use, and psychotropic drug poisonings (a proxy for suicide attempts) and suicide deaths. We assessed possible spillover to adults not targeted by the warnings. The one study that measured intended physician monitoring of suicidal thoughts and behaviors did not find evidence of an increase. Multiple studies found significant unintended reductions in mental health care after the warnings. After these reductions, there were marked increases in psychotropic drug poisonings and suicide deaths. These findings support reevaluation of risks and benefits of the FDA's black-box antidepressant warnings

Epigenetic Characterization of the FMR1 Gene and Aberrant Neurodevelopment in Human Induced Pluripotent Stem Cell Models of Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5′ untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology.FRAXA Research FoundationHarvard Stem Cell Institute (seed grant)Stanley Medical Research InstituteNational Institute of Mental Health (U.S.) (grant #R33MH087896

Inhibition of Hedgehog Signaling Antagonizes Serous Ovarian Cancer Growth in a Primary Xenograft Model

Recent evidence links aberrant activation of Hedgehog (Hh) signaling with the pathogenesis of several cancers including medulloblastoma, basal cell, small cell lung, pancreatic, prostate and ovarian. This investigation was designed to determine if inhibition of this pathway could inhibit serous ovarian cancer growth.We utilized an in vivo pre-clinical model of serous ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous ovarian tumor tissue was used to generate tumor xenografts in mice that were subsequently treated with cyclopamine or IPI-926.Both compounds demonstrated significant anti-tumor activity as single agents. When IPI-926 was used in combination with paclitaxel and carboplatinum (T/C), no synergistic effect was observed, though sustained treatment with IPI-926 after cessation of T/C continued to suppress tumor growth. Hh pathway activity was analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however, inhibited Hh signaling in both mouse stromal and human tumor cells. Expression data from the micro-dissected stroma in human serous ovarian tumors confirmed the presence of Gli1 transcript and a significant association between elevated Gli1 transcript levels and worsened survival.IPI-926 treatment inhibits serous tumor growth suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may hold promise as a novel therapeutic target, especially in the maintenance setting

Partial Meal Replacement Plan and Quality of the Diet at 1 Year: Action for Health in Diabetes (Look AHEAD) Trial

Little is known about diet quality with a reduced-energy, low-fat, partial meal replacement (PMR) plan, especially in individuals with type 2 diabetes. The Action for Health in Diabetes (Look AHEAD) trial implemented a PMR plan in the intensive lifestyle intervention (ILI)

Short-term geriatric assessment units: 30 years later

<p>Abstract</p> <p>Background</p> <p>The increasing number of hospitalized elderly persons has greatly challenged decision makers to reorganize services so as to meet the needs of this clientele. Established progressively over the last 30 years, the short-term Geriatric Assessment Unit (GAU) is a specialized care program, now implemented in all the general hospital centres in Quebec. Within the scope of a broader reflection upon the appropriate care delivery for elderly patients in our demographic context, there is a need to revisit the role of GAU within the hospital and the continuum of care. The objective of this project is to describe the range of activities offered by Quebec GAU and the resources available to them.</p> <p>Methods</p> <p>In 2004, 64 managers of 71 GAU answered a mail questionnaire which included 119 items covering their unit's operation and resources in 2002-2003. The clinical and administrative characteristics of the clientele admitted during this period were obtained from the provincial database Med-Echo. The results were presented according to the geographical location of GAU, their size, their university academic affiliation, the composition of their medical staff, and their clinical care profile.</p> <p>Results</p> <p>Overall, GAU programs admitted 9% of all patients aged 65 years and older in the surveyed year. GAU patients presented one or more geriatric syndromes, including dementia. Based on their clientele, three distinct clinical care profiles of GAU were identified. Only 19% of GAU were focused on geriatric assessment and acute care management; 23% mainly offered rehabilitation care, and the others offered a mix of both types. Thus, there was a significant heterogeneity in GAU's operation.</p> <p>Conclusions</p> <p>The GAU is at the cutting edge of geriatric services in hospital centres. Given the scarcity of these resources, it would be appropriate to better target the clientele that may benefit from them. Standardizing and promoting GAU's primary role in acute care must be reinforced. In order to meet the needs of the frail elderly not admitted in GAU, alternative care models centered on prevention of functional decline must be applied throughout all hospital wards.</p