Influences on adherence in African American women with HIV

Thesis advisor: Anne E. NorrisLittle is known about adherence among African American women with HIV. This crossectional study investigated the direct and indirect effects of subjective wellbeing (SWB), physical activity, depression, and spiritual beliefs on adherence to antiretroviral therapy, condom use, and appointment keeping in 86 participants. These variables formed a theoretical model proposed in response to findings in the literature and clinical observations. Participants completed demographic and clinical questionnaires, the Center for Adherence Support Evaluation (CASE) Adherence Index (antiretroviral therapy adherence), Satisfaction with Life scale (SWB), Paffenbarger Physical Activity Questionnaire, CES-D (Depression), the Faith subscale of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale (spiritual beliefs), and questions regarding condom use and appointment keeping. Descriptive statistics, ANOVA, t-tests, and Chi square analyses were used to analyze clinical and demographic variables, scale means, and effects on adherence variables. Linear and logistic regression analyses were used to test study hypotheses, and path analysis was used to confirm the relationships in the linear regression model. The final model for medication adherence explained 31% of the variance. SWB had a direct effect (β = .30, p < .01). Spiritual beliefs had direct (.21), and indirect effects (.07) through SWB. Having a history of hospitalization for mental illness had direct (-.25), and indirect effects (-.06) through SWB. Physical activity had only a direct effect (β = - .19, p = .05), and no effect on SWB (p = .26). Findings failed to support relationships hypothesized in the model for condom and appointment adherence, though age was shown to have a positive effect (B = 0.06, p < .05) on appointment adherence in the final model. Further research is needed to replicate these findings in a larger cohort of African American women with HIV, and to identify factors that impact condom use and appointment keeping. Study findings argue for the need to assess spiritual beliefs, connect individuals with programs designed to enhance spiritual beliefs, and other resources that may positively influence well-being and medication adherence in this population.Thesis (PhD) — Boston College, 2008.Submitted to: Boston College. Connell School of Nursing.Discipline: Nursing

Longitudinal kinematic imbalances in (anti-)neutrino interactions for improved measurements of nuclear removal energies and the axial vector form factor

Current and future accelerator neutrino oscillation experiments require an improved understanding of nuclear effects in neutrino-nucleus interactions. One important systematic uncertainty is given by potential mismodeling of the removal energy, which biases the reconstruction of the neutrino energy. In this manuscript, we introduce a novel observable for accelerator neutrino oscillation experiments, the visible longitudinal momentum imbalance, reconstructed in charged current quasi-elastic interactions from the outgoing charged lepton and nucleon. Minimally dependent on the neutrino energy and directly sensitive to the removal energy distribution, we demonstrate a method to constrain the latter. Further, we show how the use of the longitudinal imbalance in anti-neutrino interactions in a target containing hydrogen allows for an improved, high-purity selection of the interactions on hydrogen. This approach offers the potential for precise measurements of the nuclear axial vector form factor as well as of the anti-neutrino flux.Comment: 9 pages, 9 figure

Relationship Between Neck Circumference and Cardiometabolic Parameters in HIV-Infected and non–HIV-Infected Adults

OBJECTIVE: Upper body fat is associated with increased cardiometabolic risk. More recently, neck circumference (NC) and/or neck fat have been associated with hyperlipidemia, impaired glucose homeostasis, and hypertension. The objective of this study was to determine whether this relationship is evident in HIV-infected individuals, who often exhibit changes in relative fat distribution, and to determine whether NC is independently associated with carotid intima-media thickness (cIMT) in HIV and non–HIV-infected patients. RESEARCH DESIGN AND METHODS: Body composition, including anthropometrics, visceral adipose tissue assessment by CT, and metabolic parameters, including lipids, cIMT, and oral glucose tolerance test, were measured in 174 men and women with HIV infection and 154 non–HIV-infected subjects. NC was measured in triplicate inferior to the laryngeal prominence. RESULTS: In univariate analysis, NC was significantly and positively related to blood pressure, hemoglobin A1c, glucose, and insulin and significantly and negatively related to HDL cholesterol in HIV-infected individuals and HIV-negative control subjects. NC was significantly associated with cIMT in univariate regression analysis among HIV-infected (r = 0.21, P = 0.006) and non–HIV-infected (r = 0.31, P = 0.0001) patients. This relationship remained significant among non–HIV-infected patients (R2 = 0.45, P < 0.001) but not HIV-infected patients in multivariate modeling controlling for age, sex, race, smoking hypertension, glucose, and lipids. CONCLUSIONS: Among both HIV and non–HIV-infected patients, increased NC is strongly associated with decreased HDL and impaired glucose homeostasis. Among non–HIV-infected subjects, NC also predicts increased cIMT when controlling for traditional risk factors

3D-partition functions on the sphere: exact evaluation and mirror symmetry

We study N = 4 quiver theories on the three-sphere. We compute partition functions using the localisation method by Kapustin et al. solving exactly the matrix integrals at finite N, as functions of mass and Fayet-Iliopoulos parameters. We find a simple explicit formula for the partition function of the quiver tail T(SU(N)). This formula opens the way for the analysis of star-shaped quivers and their mirrors (that are the Gaiotto-type theories arising from M5 branes on punctured Riemann surfaces). We provide non-perturbative checks of mirror symmetry for infinite classes of theories and find the partition functions of the TN theory, the building block of generalised quiver theories.Comment: 30 pages, 12 figures. v2: added references, minor change

Priming for self-esteem influences the monitoring of one’s own performance

Social cues have subtle effects on a person, often without them being aware. One explanation for this influence involves implicit priming of trait associations. To study this effect, we activated implicit associations in participants of ‘being Clever’ or ‘being Stupid’ that were task relevant, and studied its behavioural impact on an independent cognitive task (the n-back task). Activating a representation of ‘Clever’ caused participants to slow their reaction times after errors on the working memory task, while the reverse pattern was seen for associations to ‘Stupid’. Critically, these behavioural effects were absent in control conditions. Using functional magnetic resonance imaging, we show that the neural basis of this effect involves the anterior paracingulate cortex (area 32) where activity tracked the observed behavioural pattern, increasing its activity during error monitoring in the ‘Clever’ condition and decreasing in the ‘Stupid’ condition. The data provide a quantitative demonstration of how implicit cues, which specifically target a person’s self-concept, influences the way we react to our own behaviour and point to the anterior paracingulate cortex as a critical cortical locus for mediating these self-concept related behavioural regulations

Factor IX Expression within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients with Severe Hemophilia B: Long-Term Follow- up Study of the B-Amaze Program

Introduction: FLT180a (verbrinacogene setparvovec) is an investigational, liver-directed AAV gene therapy for the treatment of patients with hemophilia B (HB). FLT180a consists of a novel, potent, engineered capsid (AAVS3) containing an expression cassette encoding a Factor IX (FIX) gain-of-function protein variant ('Padua'; FIX-R338L). The B-AMAZE study was designed to identify a dose of FLT180a that maintains FIX activity within the normal range (50-150%) and thereby protect patients with severe HB from spontaneous and traumatic bleeds. Methods: B-AMAZE was a multicentre, open-label Phase 1/2 clinical trial (NCT03369444; sponsored by UCL) that evaluated FLT180a dose levels using an escalating/descending adaptive design in patients with severe (FIX activity &amp;lt;1%) or moderately severe (FIX activity 1-2%) HB who were negative for AAVS3 neutralizing antibodies. A novel regimen of prophylactic corticosteroids with/without tacrolimus was implemented to mitigate the impact of vector-related transaminitis on FIX expression. Patients who completed the 26-week B-AMAZE study were eligible for the ongoing long-term follow-up study (NCT03641703; sponsored by Freeline). Results: Ten HB patients received a single dose of FLT180a. Four FLT180a doses ranging from 3.84e11 vg/kg to 1.28e12 vg/kg were assessed. As of the data cut-off date, all patients have been followed for ≥16 months. FLT180a demonstrated a favorable safety profile, without evidence of inhibitors against FIX, infusion-related or allergic reactions. The most common treatment-related adverse event was transient elevation in alanine aminotransferase. An event of AV fistula thrombosis occurred in a 67-year-old patient who received the highest dose of 1.28e12 vg/kg (total dose of 1.15e14 vg) and had supranormal FIX levels; this patient was treated with anticoagulants. While these FIX levels demonstrate the potency of our proprietary AAVS3 capsid, this dose will not be used in future hemophilia studies. At Week 26 after FLT180a administration, a dose-response relationship was observed with mean FIX activity of 45.0%, 35.5%, 141.5%, and 175.5% for 3.84e11, 6.4e11, 8.32e11, and 1.28e12 vg/kg doses, respectively (Table); FIX activity levels ≥50% were achieved in 7 of 8 patients treated with the three highest doses. One patient (Patient 4) who received 6.4e11 vg/kg lost transgene expression early due to transaminitis and resumed routine factor prophylaxis. The 8.32e11 vg/kg cohort received an extended immune management regimen (9-18 weeks) with prophylactic tacrolimus in addition to prednisolone to prevent breakthrough vector-related transaminitis. However, after cessation of the immune management regimen, transaminitis with concomitant reductions in FIX activity was observed in all patients in the 8.32e11 vg/kg cohort. The combination of prophylactic tacrolimus and prednisolone appeared to have suppressed immune-mediated transaminitis while administered, but recurrence of transaminitis developed soon after cessation. This unique and previously unreported observation suggests that the longer-duration prophylactic immune management regimen may have prevented tolerization to the vector because this was not observed in earlier cohorts where a brief course of tacrolimus was given reactively for breakthrough transaminitis. All patients (including the 8.32e11 vg/kg cohort) have achieved steady state. Patients in the earliest cohort who received the lowest dose (3.84e11 vg/kg) have shown stable FIX activity for &amp;gt;3 years. There were no spontaneous bleeds that required FIX supplementation in patients who maintained FIX activity above 50%; Patient 4 in the 6.4e11 vg/kg cohort experienced two bleeds (cause unknown) after he lost transgene expression, which were treated with exogenous FIX. One patient received exogenous FIX for treatment of a traumatic bleed, but his FIX activity level was 57% at the time of the event. Additional efficacy and safety results with &amp;gt;3.5 years of follow-up will be presented. Conclusions: B-AMAZE is the first HB gene therapy study to achieve normal levels of FIX activity using relatively low vector doses. Results suggest that a dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune management, has the potential to achieve durable FIX activity in the normal range (50-150%) and thereby prevent spontaneous bleeds and normalize hemostasis in the event of traumatic bleeds

The Vehicle, Spring 1998

Vol. 39, No. 2 Table of Contents The MarriageStephanie Kavanaughpage 10 UntitledKyla Anthonypage 11 Behind the Old Farmhouse FieldJacob Tolbertpage 12 decomposing tearsDavid Moutraypage 13 brookBrooke Tidballpage 14 Sacred CircleJacob Tolbertpage 15 without discretionMandy Watsonpage 16 HAIRCUTStephanie Kavanaughpage 17 Slave for a DayLizz Lampherepage 18 Taco HellEric Dolanpage 19 Who Am I?Sara Cizmarpage 20 XXJason Brownpage 21-22 Torn PaperJacob Tolbertpage 23-24 Fat GirlsKim Hunterpage 24 UntitledMaureen Rafterypage 25 LegosA. Fijakiewiczpage 26 Black Shoes in JuneErin Maagpage 27 UntitledMaureen Rafterypage 28 TicklishLizz Lampherepage 29 of naiveteMandy Watsonpage 30 The Geology of WaterfallsStephanie Kavanaughpage 31 GratitudeJeanette McCainpage 32 AnswersKim Hunterpage 33 Cornfield MeetDaniel G. Fitzgeraldpage 39https://thekeep.eiu.edu/vehicle/1071/thumbnail.jp

The role of de-excitation in the final-state interactions of protons in neutrino-nucleus interactions

Present and next generation of long-baseline accelerator experiments are bringing the measurement of neutrino oscillations into the precision era with ever-increasing statistics. One of the most challenging aspects of achieving such measurements is developing relevant systematic uncertainties in the modeling of nuclear effects in neutrino-nucleus interactions. To address this problem, state-of-the-art detectors are being developed to extract detailed information about all particles produced in neutrino interactions. To fully profit from these experimental advancements, it is essential to have reliable models of propagation of the outgoing hadrons through nuclear matter able to predict how the energy is distributed between all the final-state observed particles. In this article, we investigate the role of nuclear de-excitation in neutrino-nucleus scattering using two Monte Carlo cascade models: NuWro and INCL coupled with the de-excitation code ABLA. The ablation model ABLA is used here for the first time to model de-excitation in neutrino interactions. As input to ABLA, we develop a consistent simulation of nuclear excitation energy tuned to electron-scattering data. The paper includes the characterization of the leading proton kinematics and of the nuclear cluster production during cascade and de-excitation. The observability of nuclear clusters as vertex activity and their role in a precise neutrino energy reconstruction is quantified.Comment: 14 pages, 13 figure

PfRH5: A Novel Reticulocyte-Binding Family Homolog of Plasmodium falciparum that Binds to the Erythrocyte, and an Investigation of Its Receptor

Multiple interactions between parasite ligands and their receptors on the human erythrocyte are a condition of successful Plasmodium falciparum invasion. The identification and characterization of these receptors presents a major challenge in the effort to understand the mechanism of invasion and to develop the means to prevent it. We describe here a novel member of the reticulocyte-binding family homolog (RH) of P. falciparum, PfRH5, and show that it binds to a previously unrecognized receptor on the RBC. PfRH5 is expressed as a 63 kDa protein and localized at the apical end of the invasive merozoite. We have expressed a fragment of PfRH5 which contains the RBC-binding domain and exhibits the same pattern of interactions with the RBC as the parent protein. Attachment is inhibited if the target cells are exposed to high concentrations of trypsin, but not to lower concentrations or to chymotrypsin or neuraminidase. We have determined the affinity, copy number and apparent molecular mass of the receptor protein. Thus, we have shown that PfRH5 is a novel erythrocyte-binding ligand and the identification and partial characterization of the new RBC receptor may indicate the existence of an unrecognized P. falciparum invasion pathwa