89 research outputs found

    Correlation of expression of BP1, a homeobox gene, with estrogen receptor status in breast cancer

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    BACKGROUND: BP1 is a novel homeobox gene cloned in our laboratory. Our previous studies in leukemia demonstrated that BP1 has oncogenic properties, including as a modulator of cell survival. Here BP1 expression was examined in breast cancer, and the relationship between BP1 expression and clinicopathological data was determined. METHODS: Total RNA was isolated from cell lines, tumors, and matched normal adjacent tissue or tissue from autopsy. Reverse transcription polymerase chain reaction was performed to evaluate BP1 expression. Statistical analysis was accomplished with SAS. RESULTS: Analysis of 46 invasive ductal breast tumors demonstrated BP1 expression in 80% of them, compared with a lack of expression in six normal breast tissues and low-level expression in one normal breast tissue. Remarkably, 100% of tumors that were negative for the estrogen receptor (ER) were BP1-positive, whereas 73% of ER-positive tumors expressed BP1 (P = 0.03). BP1 expression was also associated with race: 89% of the tumors of African American women were BP1-positive, whereas 57% of those from Caucasian women expressed BP1 (P = 0.04). However, there was no significant difference in BP1 expression between grades I, II, and III tumors. Interestingly, BP1 mRNA expression was correlated with the ability of malignant cell lines to cause breast cancer in mice. CONCLUSION: Because BP1 is expressed abnormally in breast tumors, it could provide a useful target for therapy, particularly in patients with ER-negative tumors. The frequent expression of BP1 in all tumor grades suggests that activation of BP1 is an early event

    Creative destruction in science

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    Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

    On-site primary care and mental health services in outpatient drug abuse treatment units

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    Providing health services to drug abuse treatment clients improves their outcomes. Using data from a 1995 national survey of 597 outpatient drug abuse treatment units, this article examines the relationship between these units' organizational features and the degree to which they provided onsite primary care and mental health services. In two-stage models, Joint Commission on Accreditation of Healthcare Organizations-certified and methadone programs delivered more on-site primary care services. Units affiliated with mental health centers provided more on-site mental health services but less direct medical care. Units with more dual-diagnosis clients provided more on-site mental health but fewer on-site HIV/AIDS treatment services. Organizational features appear to influence the degree to which health services are incorporated into drug abuse treatment. Fully integrated care might be an unattainable ideal for many such organizations, but quality improvement across the treatment system might increase the reliability of clients' access to health services.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45768/1/11414_2005_Article_BF02287796.pd

    Cross Adaptation - Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia

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    To prepare for extremes of heat, cold or low partial pressures of O2, humans can undertake a period of acclimation or acclimatization to induce environment specific adaptations e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. Whilst these strategies are effective, they are not always feasible, due to logistical impracticalities. Cross adaptation is a term used to describe the phenomenon whereby alternative environmental interventions e.g. HA, or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate intensity exercise at altitude via adaptations allied to improved oxygen delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on oxygen delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross tolerance. The effects of CA on markers of cross tolerance is an area requiring further investigation. Because much of the evidence relating to cross adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross adaptation between heat and altitude, and between cold and altitude, is warranted, as is exploration of benefits across different populations and physical activity profiles

    Jail-based reentry programming to support continued treatment with medications for opioid use disorder: Qualitative perspectives and experiences among jail staff in Massachusetts

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    Background: Individuals with opioid use disorder released to communities after incarceration experience an elevated risk for overdose death. Massachusetts is the first state to mandate county jails to deliver all FDA approved medications for opioid use disorder (MOUD). The present study considered perspectives around coordination of post-release care among jail staff engaged in MOUD programs focused on coordination of care to the community. Methods: Focus groups and semi-structured interviews were conducted with 61 jail staff involved in implementation of MOUD programs. Interview guide development, and coding and analysis of qualitative data were guided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Deductive and inductive approaches were used for coding and themes were organized using the EPIS. Results: Salient themes in the inner context focused on the elements of reentry planning that influence coordination of post-release care including timing of initiation, staff knowledge about availability of MOUD in community settings, and internal collaborations. Findings on bridging factors highlighted the importance of interagency communication to follow pre-scheduled release dates and use of bridge scripts to minimize the gap in treatment during the transition. Use of navigators was an additional factor that influenced MOUD initiation and engagement in community settings. Outer context findings indicated partnerships with community providers and timely reinstatement of health insurance coverage as critical factors that influence coordination of post-release care. Conclusions: Coordination of MOUD post-release continuity of care requires training supporting staff in reentry planning as well as resources to enhance internal collaborations and bridging partnerships between in-jail MOUD programs and community MOUD providers. In addition, efforts to reduce systemic barriers related to unanticipated timing of release and reinstatement of health insurance coverage are needed to optimize seamless post-release care. Keywords: EPIS framework; Jails; Medication for opioid use disorder; Opioid use disorder; Post-release coordination of care

    The relationship of Medicaid expansion to psychiatric comorbidity care within substance use disorder treatment programs

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    BACKGROUND: Co-occurring mental health disorders are common among substance use disorder (SUD) patients. Medicaid expansion aimed to reduce barriers to SUD and mental health care and thereby improve treatment outcomes. METHODS: We estimated change in the proportion of United States SUD treatment sites offering treatment for psychiatric comorbidities following Medicaid expansion as part of implementation of the Affordable Care Act (ACA) in 2014. Using panel data from the 2013-2014, n = 660, and 2016-2017, n = 638, waves of the National Drug Abuse Treatment System Survey (NDATSS), we estimated change in the proportion of sites offering antidepressant medication, other psychiatric medication, behavioral treatment, or any combination thereof for treatment of mental health comorbidities (i.e., beyond services focused on SUD). We modeled the impact of Medicaid expansion as an interaction between year and date of Medicaid expansion. We constructed a mixed-effects linear regression model for each outcome, with the interaction variable as the main exposure, site as a random effect, and site\u27s average duration of treatment, proportion of clients with psychiatric comorbidities, average caseload per treatment prescribing-clinician on staff, type of facility and geographic region as covariates, to estimate a difference-in-differences (D-I-D) equation. RESULTS: The adjusted D-I-D analysis indicated that the proportion of SUD treatment sites offering antidepressants for psychiatric treatment increased 10% (95% CI 1%, 18%) in the Medicaid expansion sites compared to non-expansion sites. The D-I-D for other psychiatric medications was also 10% (95% 1%, 19%). No significant changes were observed in behavioral treatment or the combination measure. The strongest association between Medicaid expansion and offering medication for mental health comorbidities was the 34% increase observed for residential treatment settings (95% CI 10%, 59%). CONCLUSION: Availability of psychiatric medication treatment in SUD treatment settings increased following Medicaid expansion, particularly in residential SUD facilities. This policy change has facilitated integrated treatment for the substantial share of SUD treatment patients with mental health comorbidities, with the greatest benefit for patients receiving SUD treatment in residential programs

    I\u27ve been to more of my friends\u27 funerals than I\u27ve been to my friends\u27 weddings : Witnessing and responding to overdose in rural Northern New England

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    Purpose: Overdose is a leading cause of death among people who use drugs (PWUDs), but policies to reduce fatal overdose have had mixed results. Summaries of naloxone access and Good Samaritan Laws (GSLs) in prior studies provide limited information about local context. Witnessing overdoses may also be an important consideration in providing services to PWUDs, as it contributes to post traumatic stress disorder (PTSD) symptoms, which complicate substance use disorder treatment. Methods: We aim to estimate the prevalence and correlates of witnessing and responding to an overdose, while exploring overdose context among rural PWUD. The Drug Injection Surveillance and Care Enhancement for Rural Northern New England (DISCERNNE) mixed-methods study characterized substance use and risk behaviors in 11 rural Massachusetts, Vermont, and New Hampshire counties between 2018 and 2019. PWUD completed surveys (n = 589) and in-depth interviews (n = 22). Findings: Among the survey participants, 84% had ever witnessed an overdose, which was associated with probable PTSD symptoms. Overall, 51% had ever called 911 for an overdose, though some experienced criminal legal system consequences despite GSL. Although naloxone access varied, 43% had ever used naloxone to reverse an overdose. Conclusions: PWUD in Northern New England commonly witnessed an overdose, which they experienced as traumatic. Participants were willing to respond to overdoses, but faced barriers to effective overdose response, including limited naloxone access and criminal legal system consequences. Equipping PWUDs with effective overdose response tools (education and naloxone) and enacting policies that further protect PWUDs from criminal legal system consequences could reduce overdose mortality. Keywords: Good Samaritan Laws; New England; naloxone access; opioid overdose; rural health
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