Finding Success in Failure: Using Latent Profile Analysis to Examine Heterogeneity in Psychosocial Functioning Among Heavy Drinkers Following Treatment

Aims- To estimate differences in post-treatment psychosocial functioning among treatment failures\u27 (i.e. heavy drinkers, defined as 4+/5+ drinks for women/men) from two large multi-site clinical trials and to compare these levels of functioning to those of the purported treatment successes\u27 (i.e. non-heavy drinkers). Design- Separate latent profile analyses of data from two of the largest alcohol clinical trials conducted in the United States, COMBINE (Combined Pharmacotherapies and Behavioral Interventions) and Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity), comparing psychosocial outcomes across derived classes of heterogeneous treatment responders. Setting- Eleven US academic sites in COMBINE, 27US treatment sites local to nine research sites in Project MATCH. ParticipantsA total of 962 individuals in COMBINE (69% male, 77% white, mean age: 44years) treated January 2001 to January 2004 and 1528 individuals in Project MATCH (75% male, 80% white, mean age: 40years) treated April 1991 to September 1994. MeasurementsIn COMBINE, we analyzed health, quality of life, mental health symptoms and alcohol consequences 12 months post-baseline. In Project MATCH, we examined social functioning, mental health symptoms and alcohol consequences 15 months post-baseline. Findings- Latent profile analysis of measures of functioning in both samples supported a three-profile solution for the group of treatment failures\u27, characterized by high-, average- and low-functioning individuals. The high-functioning treatment failures\u27 generally performed better across measures of psychosocial functioning at follow-up than participants designated treatment successes\u27 by virtue of being abstainers or light drinkers. Conclusions- Current United States Food and Drug Administration guidance to use heavy drinking as indicative of treatment failure\u27 fails to take into account substantial psychosocial improvements made by individuals who continue occasionally to drink heavily post-treatment

Polyphenon E enhances the antitumor immune response in neuroblastoma by inactivating myeloid suppressor cells

This is the author's accepted manuscript. The final published article is available from the link below. Note: In this manuscript as well as in the original published version of this article the word "Polyphenon" was incorrectly spelled in the title as "Polyphenol."Purpose: Neuroblastoma is a rare childhood cancer whose high risk, metastatic form has a dismal outcome in spite of aggressive therapeutic interventions. The toxicity of drug treatments is a major problem in this pediatric setting. In this study, we investigated whether Polyphenon E, a clinical grade mixture of green tea catechins under evaluation in multiple clinical cancer trials run by the National Cancer Institute (Bethesda, MD), has anticancer activity in mouse models of neuroblastoma. Experimental Design: We used three neuroblastoma models: (i) transgenic TH-MYCN mouse developing spontaneous neuroblastomas; (ii) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenotransplanted with human SHSY5Y cells; and (iii) A/J mice transplanted with syngeneic Neuro 2A cells. Mice were randomized in control and Polyphenon E–drinking groups. Blood from patients with neuroblastoma and normal controls was used to assess the phenotype and function of myeloid cells. Results: Polyphenon E reduced the number of tumor-infiltrating myeloid cells, and inhibited the development of spontaneous neuroblastomas in TH-MYCN transgenic mice. In therapeutic models of neuroblastoma in A/J, but not in immunodeficient NOD/SCID mice, Polyphenon E inhibited tumor growth by acting on myeloid-derived suppressor cells (MDSC) and CD8 T cells. In vitro, Polyphenon E impaired the development and motility of MDSCs and promoted differentiation to more neutrophilic forms through the 67 kDa laminin receptor signaling and induction of granulocyte colony-stimulating factor. The proliferation of T cells infiltrating a patient metastasis was reactivated by Polyphenon E. Conclusions: These findings suggest that the neuroblastoma-promoting activity of MDSCs can be manipulated pharmacologically in vivo and that green tea catechins operate, at least in part, through this mechanism.SPARKS, Research in Childhood Cancer, the CGD Research Trust, and the Wellcome Trust

Legitimacy, illegitimacy and sovereignty in Shakespeare's British plays

'Legitimacy, Illegitimacy and Sovereignty in Shakespeare's British Plays' demonstrates how Shakespeare participates in an early modern 'discourse of legitimacy' as described by Robert Zaller. This thesis, however, proposes an interrelated discourse of illegitimacy that is of equal importance to the discourse of legitimacy. A continuum or spectrum of legitimacy values is hypothesised, and seventeenth century optical illusions known as the curious perspective are used as a visual model that defines the inseparable nature of illegitimacy and legitimacy. Illegitimacy was a state traditionally defined as restrictive, and stereotyped as stigmatised by historians. Examination of the situation of early modern illegitimates in England, however, suggests a more inclusive attitude to illegitimates than has been previously acknowledged.The plays under discussion are under studied as a group; the thesis examines the British-set history and romance plays, defining them as 'British plays'. This is because one of the central implications of the discourse of (il)legitimacy is that it forms an evaluation of nationhood in early modern England and Britain. Using recent reconsiderations of national identity during the sixteenth and seventeenth centuries, this thesis identifies a strong national sentiment in Shakespeare's drama. The change from an Elizabethan English monarchy to a Jacobean British one instigated a reconsideration of what national identity might entail, using the discourse of legitimacies and illegitimacies to evaluate this developing concept. 'Legitimacy, Illegitimacy and Sovereignty in Shakespeare's British Plays' identifies how these discourses also link to other related themes in the British plays. The concept of sovereignty, as the thesis title suggests, is strongly linked to ideas of legitimacy and illegitimacy, with examples of the discourse used in this context drawn from Shakespeare's works and a wider range of texts. Identification of the sovereign with national allegiance, to a certain degree, links these themes, yet Shakespeare also dramatises an independent national sentiment in the British plays, revealing developing nationhood onstage. National sentiment also infuses another area in which the discourse of (il)legitimacy is used by Shakespeare; the legal debates of the era are reflected in the British plays; a contemporary conflict between common and civil law, and the aim of many lawyers to rediscover an ancient constitution of Britain, especially in the area of patrilinear inheritance, is acknowledged throughout in Shakespeare's use of legitimacy images and metaphors. As 'metaphors' suggests, illegitimacy is an increasingly conceptual issue in the thesis. Shakespeare uses ideas of illegitimacy to inform many areas; in particular a kind of validity or truth. A chapter on metaphorical illegitimacy demonstrates how illegitimacy and legitimacy language is suggestive of other issues. The invalidity of a usurped kingdom, a false kingship, is negotiated through illegitimacy discourses in Richard II, as the attempt to validate leadership in the second tetralogy is articulated with a discourse of totalising masculine legitimacy. 'Legitimacy, Illegitimacy and Sovereignty in Shakespeare's British Plays' works within a contextual framework to locate the language and concepts Shakespeare dramatises in a wider environment, reflecting the issues of law, sovereignty and nation that existed in early modern English and British society.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Taste Manipulation and Swallowing Mechanics in Trauma-Related Sensory-Based Dysphagia

Purpose: This study explored the effects of highconcentration taste manipulation trials on swallow function in persons with sensory-based dysphagia. Method: Dysphagia researchers partnered with clinical providers to prospectively identify traumatically injured U.S. military service members (N = 18) with sensorybased dysphagia as evidenced by delayed initiation and/or decreased awareness of residue/penetration/ aspiration. Under videofluoroscopy, participants swallowed trials of 3 custom-mixed taste stimuli: unflavored (40% weight/volume [wt/vol] barium sulfate in distilled water), sour (2.7%wt/vol citric acid in 40% wt/vol barium suspension), and sweet–sour (1.11% wt/vol citric acid plus 8% wt/vol sucrose in 40% wt/vol barium suspension). Trials were analyzed and compared via clinical rating tools (the Modified Barium Swallow Impairment Profile [Martin-Harris et al., 2008] and the Penetration-Aspiration Scale [Rosenbek, Robbins, Roecker, Coyle, & Wood, 1996]). Additionally, a computational analysis of swallowing mechanics (CASM) was applied to a subset of 9 swallows representing all 3 tastants from 3 participants. Results: Friedman’s tests for the 3 stimuli revealed significantly (p \u3c .05) improved functional ratings for Penetration-Aspiration Scale and pharyngoesophageal opening. CASM indicated differences in pharyngeal swallowing mechanics across all tastant comparisons (p ≤ .0001). Eigenvectors revealed increased tongue base retraction, hyoid elevation, and pharyngeal shortening for sweet–sour and, to a lesser extent, sour than for unflavored boluses. Conclusion: Advantageous changes in certain parameters of oropharyngeal swallowing physiology were noted with high-intensity tastants per both clinical ratings and subsequent CASM, suggesting potential therapeutic application for taste manipulation

SUPPORT for ME: Provider Focus Group Summary

This summary highlights feedback from focus groups with providers across Maine who currently address the needs of persons with substance use disorder (SUD). These providers represent individuals working in the following organizations: Health Systems, Behavioral Health Agencies, Residential Treatment, Community Recovery Programs, Opioid Treatment Programs (OTP), Emergency Medical Services (EMS), First Responders (EMT, fire, police), and law enforcement (e.g., Sheriff’s Office, Corrections). This summary report is designed to provide feedback to the Office of MaineCare Services to help inform their strategic planning process to increase statewide capacity for SUD treatment and recovery service capacity to better meet the needs of individuals with SUD in Maine. The focus group interview guide was designed to assess critical domains of interest for the state, which include current and potential provider capacity; referral capacity; access to care & service delivery; provider willingness; and administrative & procedural policies. Key Highlights from the interviews indicated that: Telehealth has emerged as a major facilitator to treatment access at all levels of care and should continue to be a reimbursed service for SUD treatment, where appropriate. Emergency rooms and jails are at the forefront for Medication Assisted Treatment (MAT) induction for OUD. While these are excellent models for care in Maine, particularly for engaging vulnerable populations in treatment, they should be used in concert with a broad spectrum of community-based services. Co-located services and effective communications across service providers are integral to creating a robust continuum of care for SUD in Maine. Staffing shortages coupled with reimbursement rates for some SUD services including outpatient therapy, residential treatment, medically supervised withdrawal services and intensive outpatient treatment programs affect the quality as well as availability of providers, and impact access to services statewide. The need for medically supervised withdrawal services is dire in Maine. Increased awareness and training opportunities to help alleviate stigma, including peer mentorship from other providers and colleagues, would help build provider capacity to treat and refer patients with SUD. For more information, please contact M. Lindsey Smith, PhD., at [email protected]

SUPPORT for ME: Key Stakeholder Interview Summary

This summary feedback report is organized to inform the Office of MaineCare Services goal of addressing barriers and finding new and/or improved ways to increase capacity in Maine for people who seek treatment and recovery services for substance use disorder. Interview protocols were designed to assess critical domains of interest for the state, which include: current and potential provider capacity, access to care & service delivery provider willingness, and financial/ administrative policies. Key Highlights from the stakeholder interviews indicated that: While there have been improvements in the integration of care for persons with behavioral health (BH) diagnoses, this integration has not fully synced with substance use disorder (SUD) services in Maine; better integration of BH and SUD is needed. Behavioral Health Homes and Opioid Health Homes are regarded as excellent models of care, and many key stakeholders would like to see this model of care expand for all members with a diagnosis of SUD. Low reimbursement rates for some SUD services including outpatient therapy, residential treatment, medically supervised withdrawal services and intensive outpatient treatment programs affect the quality of workforce, available services, and hinders capacity building efforts. Stigma exists regarding serving the population with SUD, at all levels- from state policymakers, to providers, and to the community. Maine lacks what some consider as basic SUD service options available elsewhere (e.g., variety of medication assisted-withdrawal services, plus intermediate levels of care). For more information, please contact M. Lindsey Smith, PhD, at [email protected]

An assessment of the population of cotton-top tamarins (Saguinus oedipus) and their habitat in Colombia

Numerous animals have declining populations due to habitat loss, illegal wildlife trade, and climate change. The cotton-top tamarin (Saguinus oedipus) is a Critically Endangered primate species, endemic to northwest Colombia, threatened by deforestation and illegal trade. In order to assess the current state of this species, we analyzed changes in the population of cotton-top tamarins and its habitat from 2005 to 2012. We used a tailor-made "lure strip transect" method to survey 43 accessible forest parcels that represent 30% of the species' range. Estimated population size in the surveyed region was approximately 2,050 in 2005 and 1,900 in 2012, with a coefficient of variation of approximately 10%. The estimated population change between surveys was -7% (a decline of approximately 1.3% per year) suggesting a relatively stable population. If densities of inaccessible forest parcels are similar to those of surveyed samples, the estimated population of cotton-top tamarins in the wild in 2012 was 6,946 individuals. We also recorded little change in the amount of suitable habitat for cotton-top tamarins between sample periods: in 2005, 18% of surveyed forest was preferred habitat for cotton-top tamarins, while in 2012, 17% percent was preferred. We attribute the relatively stable population of this Critically Endangered species to increased conservation efforts of Proyecto Tití, conservation NGOs, and the Colombian government. Due to continued threats to cotton-top tamarins and their habitat such as agriculture and urban expansion, ongoing conservation efforts are needed to ensure the long-term survival of cotton-top tamarins in Colombia.Publisher PDFPeer reviewe

HOUSE: Homeless Opioid User Service Engagement Program. Year 1 Report

Homelessness and lack of stable housing is often a barrier to achieving stability for individuals who are experiencing homelessness (IWAEH) with an OUD. In order to meet the complex needs of IWAEH with OUD, the Department of Health and Human Services funded a pilot program in 2021, the Homeless Opioid Users Service Engagement (HOUSE) Program; clinicians at Greater Portland Health provide clients with low-barrier Medication Assisted Treatment (MAT), while staff at Preble Street provide casework support and rapid housing assistance to individuals who have been identified as being at high risk of overdose, are experiencing homelessness, and are diagnosed with an OUD. . The services resulting from this pilot are intended to provide comprehensive treatment, case management, housing services and peer support in an effort to support long-term recovery and reduced opioid related morbidity and mortality among IWAEH with OUD. The primary goals of the HOUSE Program evaluation are to: (1) document implementation strategies and identify barriers and facilitators to implementation; (2) evaluate the efficacy of the intervention strategies at increasing access to prevention, treatment and recovery supports for IWAEH with OUD; (3) examine the impact of housing liaison services and Assistance Funds on housing stability among IWAEH with OUD; (4) assess the cost effectiveness and return on investment of the intervention strategies and (5) examine the impact of the intervention strategies on participant engagement and outcomes. Early learnings from the mixed methods approach indicate that the first year of the initiative demonstrate that while there remain challenges to engaging this population, the use of evidence-based treatments in combination with intensive case management and peer supports can be an effective way to maintain stabilize patients and address both their medical and housing needs