Maltreatment, psychiatric symptoms and human immunodeficiency virus/sexual transmitted infection risk behavior among youth with alcohol and other drug use problems: A person-centered analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). ^ LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth. ^

Characterizing Internet worm spatial-temporal infection structures

Since the Morris worm was released in 1988, Internet worms continue to be one of top security threats. For example, the Conficker worm infected 9 to 15 million machines in early 2009 and shut down the service of some critical government and medical networks. Moreover, it constructed a massive peer-to-peer (P2P) botnet. Botnets are zombie networks controlled by attackers setting out coordinated attacks. In recent years, botnets have become the number one threat to the Internet. The objective of this research is to characterize spatial-temporal infection structures of Internet worms, and apply the observations to study P2P-based botnets formed by worm infection. First, we infer temporal characteristics of the Internet worm infection structure, i.e., the host infection time and the worm infection sequence, and thus pinpoint patient zero or initially infected hosts. Specifically, we apply statistical estimation techniques on Darknet observations. We show analytically and empirically that our proposed estimators can significantly improve the inference accuracy. Second, we reveal two key spatial characteristics of the Internet worm infection structure, i.e., the number of children and the generation of the underlying tree topology formed by worm infection. Specifically, we apply probabilistic modeling methods and a sequential growth model. We show analytically and empirically that the number of children has asymptotically a geometric distribution with parameter 0.5, and the generation follows closely a Poisson distribution. Finally, we evaluate bot detection strategies and effects of user defenses in P2P-based botnets formed by worm infection. Specifically, we apply the observations of the number of children and demonstrate analytically and empirically that targeted detection that focuses on the nodes with the largest number of children is an efficient way to expose bots. However, we also point out that future botnets may self-stop scanning to weaken targeted detection, without greatly slowing down the speed of worm infection. We then extend the worm spatial infection structure and show empirically that user defenses, e.g. , patching or cleaning, can significantly mitigate the robustness and the effectiveness of P2P-based botnets. To counterattack, we evaluate a simple measure by future botnets that enhances topology robustness through worm re-infection.

Bahamian men's sexual risks for HIV infection

Heterosexual adult men have been a neglected population that is at risk for HIV infection. In an era burdened by the devastation caused by HIV, it is alarming that risky sexual behavior continues to be a problem among heterosexuals. Heterosexual sexual behavior has contributed to a growing trend of HIV transmission in the Caribbean where the average prevalence in the adult population is 5%. Despite the availability of condoms and HIV prevention efforts of many Caribbean public health departments to reduce the spread of the disease, there appears to be barriers to safer sex practices. Guided by the theory of planned behavior, a descriptive correlational design was used with 185 Bahamian men ages 18 years and older to (a) examine the relationships among select demographics, masculine ideology, condom attitudes, self-efficacy for condom use, and safer sex behaviors; and (b) identify select predictors of condom use among Bahamian men. Data were collected using four standardized instruments and a demographic questionnaire. The results of this study suggest that masculine ideology, condom attitudes, and condom use self-efficacy are important in explaining 33% variance in safer sex behaviors among Bahamian men. Income (β = −.15, p < .01), masculine ideology (β = −.24, p < .01), condom attitudes, (β = .36, p < .01), and condom use self-efficacy (β = .1, p < .01) were significantly associated with safer sex behaviors. The empirical knowledge obtained from this study will be used to provide a rationale for nurses and policy makers to design and conduct culturally sensitive interventions with an aim of achieving an increase in safer sex behaviors among Bahamian men.^

Interactive Effects of Morphine on HIV Infection: Role in HIV-Associated Neurocognitive Disorder

HIV epidemic continues to be a severe public health problem and concern within USA and across the globe with about 33 million people infected with HIV. The frequency of drug abuse among HIV infected patients is rapidly increasing and is another major issue since injection drug users are at a greater risk of developing HIV associated neurocognitive dysfunctions compared to non-drug users infected with HIV. Brain is a major target for many of the recreational drugs and HIV. Evidences suggest that opiate drug abuse is a risk factor in HIV infection, neural dysfunction and progression to AIDS. The information available on the role of morphine as a cofactor in the neuropathogenesis of HIV is scanty. This review summarizes the results that help in understanding the role of morphine use in HIV infection and neural dysfunction. Studies show that morphine enhances HIV-1 infection by suppressing IL-8, downregulating chemokines with reciprocal upregulation of HIV coreceptors. Morphine also activates MAPK signaling and downregulates cAMP response element-binding protein (CREB). Better understanding on the role of morphine in HIV infection and mechanisms through which morphine mediates its effects may help in devising novel therapeutic strategies against HIV-1 infection in opiate using HIV-infected population.

Maltreatment, Psychiatric Symptoms and Human Immunodeficiency Virus/Sexual Transmitted Infection Risk Behavior Among Youth with Alcohol and Other Drug Use Problems: A Person-Centered Analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth.

Process inventory and pollution prevention overview for the citrus industry

Florida citrus represents approximately 70 percent of the industry production in the United States; therefore, any associated agricultural and industrial contamination is of concern and a focus of attention. The use of synthetic organic chemicals has become a farmer's necessity in order to supply consumers with high quality products, free of pest damage. However, industrial citrus wastes and chemical residual levels worry not only government agencies but also consumers since they indicate a serious habitat risk. This study assesses citrus industrial processes and the paths that chemical substances follow from the time the citrus seed is planted until consumers get a final product as either fresh fruit or processed product. The study is built on information from United States Environmental Protection Agency (US EPA) manuals, Dade County Environmental Resources Management (DERM) inspection records, United States Food and Drug Administration (US FDA) regulations, Florida standards, journal publications, and research reports. Pollution prevention (P2 or prevention-of-pollution) alternatives are identified; alternatives are proposed, evaluated, and included. Strategies are described and pollution prevention opportunities proposed to minimize citrus wastes generation, chemical residuals in products, their environmental impact and health risk aspects while maximizing product quality.

HIV/AIDS: um perfil epidemiológico do vírus e uma análise das práticas seguras, conhecimento e percepção de mulheres

In recent decades, the debate surrounding the consequences of the HIV has passed by great changes. Earlier, prevention campaigns focused risk groups then risk behaviors and ultimately vulnerability. Furthermore, over the years, the dimensions of HIV that emerged in the social environment are these: internalization, heterosexualization, impoverishment and feminization. Based on these contexts, the composition of this study comprises two papers: the former has the overall objective to analyze the epidemiology and incidence of HIV in Brazilian regions in the period from 1980 to 2012; the latter, it aims to find out whether there is the relationship among safe practices, knowledge and perception of women residents in Manaus and Boa Vista cities on the infection by HIV. In paper 1, it was used information from the Health Ministry, as a data source. Besides, it was developed an exploratory and spatial analysis of incidence rates and relative proportion of notified cases. In paper 2, was used as a source of data, the research "Evaluating the process of spatial and epidemic diffusion of HIV in the federal units of Brazil-Northern Region" in 2008. Furthermore, Statistical Techniques of Cluster Analysis, Analysis of Variance, Chi-Square and Logistic Regression were applied. In this paper, it was found that, in Brazilian Regions, the prevalence of reported cases occurred among heterosexuals in men 20-40 year age group and residing in metropolitan areas. It was observed a significant spatial correlation of the incidence rate of reported cases of HIV. It was also noted by the results that have good knowledge and awareness about HIV does not imply, essentially, in a safe sexual intercourse. These results have shown the need public policies geared to the guiding of society, based in educational strategies aiming both information about the virus and its prevention, as well as public awareness for safe sex practices or in stable or not intercourses

CAUTI prevention bundles: improving best practices within Western Health for continued success

Background: Persons in acute care settings who have indwelling urethral catheters are at higher risk of acquiring a urinary tract infection (UTI). Other complications related to prolonged indwelling urinary catheters include decreased mobility, damage to the meatus and/or urethra, increase use of antibiotics, increased length of stay, and pain. UTIs in acute care settings account for 30 to 40% of all health care associated infections (HAIs). Of these, 80% are catheter associated UTIs (CAUTIs). Purpose: To utilized the CDC (2009) bundle approach for CAUTI prevention and create a program which supports a multimodal method to improving urinary catheter use, maintenance, and removal, including a continuing competency program where role expansion is anticipated. Methods: A comprehensive review of the literature was conducted. Physicians were consulted through a power point presentation followed by a letter explaining the project, a questionnaire, and two selections of relevant literature. Nursing staff and allied health professionals from the target units of 3A and 3B medicine attended one of two lunch and learns. They were presented the project via a power point presentation and the same questionnaire as distributed to physicians. Results: Five e-learning modules, a revised policy, and clinical pathway have been developed to support staff with best practice knowledge transfer. Conclusion: Behaviour changes need to be approached with a framework, extensive consultation, and education. Sustainability of any practice change cannot occur without having completed the background work to ensure staff have access to tools to support the change.

Evaluating the Impact of the Positive Choices Intervention on Substance Use, Psychological, and Care Engagement Outcomes Relevant to Current National HIV Prevention Goals

The HIV epidemic in the United States continues to be a significant public health problem, with approximately 50,000 new infections occurring each year. National public health priorities have shifted in recent years towards targeted HIV prevention efforts among people living with HIV/AIDS (PLWHA) that include: increasing engagement in and retention in care, improving HIV treatment adherence, and increasing screening for and treatment of substance use and psychological difficulties. This study evaluated the efficacy of Positive Choices (PC), a brief, care-based, theory-driven, 3-session counseling intervention for newly HIV-diagnosed men who have sex with men (MSM), in the context of current national HIV prevention priorities. The study involved secondary analysis of data from a preliminary efficacy trial of the PC intervention (n=102). Descriptive statistics examined baseline substance use, psychological characteristics and strategies, and care engagement and HIV-related biological outcomes. Generalized Estimating Equations (GEE) examined longitudinal changes in these variables by study condition. Results indicated that PC improved adherence to HIV treatment, but increased use of illicit drugs, specifically amyl nitrates and other stimulant drugs; additionally, moderation analyses indicated differences in patterns of change over time in viral load by baseline depression status. Implications of the findings and suggestions for future research are discussed.

Development of tumour imaging and therapy strategies utilising unengineered bacteria

The ability of systemically administered bacteria to target and replicate to high numbers within solid tumours is well established. Tumour localising bacteria can be exploited as biological vehicles for the delivery of nucleic acid, protein or therapeutic payloads to tumour sites and present researchers with a highly targeted and safe vehicle for tumour imaging and cancer therapy. This work aimed to utilise bacteria to activate imaging probes or prodrugs specifically within target tissue in order to facilitate the development of novel imaging and therapeutic strategies. The vast majority of existing bacterial-mediated cancer therapy strategies rely on the use of bacteria that have been genetically modified (GM) to express genes of interest. While these approaches have been shown to be effective in a preclinical setting, GM presents extra regulatory hurdles in a clinical context. Also, many strains of bacteria are not genetically tractably and hence cannot currently be engineered to express genes of interest. For this reason, the development of imaging and therapeutic systems that utilise unengineered bacteria for the activation of probes or drugs represents a significant improvement on the current gold standard. Endogenously expressed bacterial enzymes that are not found in mammalian cells can be used for the targeted activation of imaging probes or prodrugs whose activation is only achieved in the presence of these enzymes. Exploitation of the intrinsic enzymatic activity of bacteria allows the use of a wider range of bacteria and presents a more clinically relevant system than those that are currently in use. The nitroreductase (NTR) enzymes, found only in bacteria, represent one such option. Chapter 2 introduces the novel concept of utilising native bacterial NTRs for the targeted activation of the fluorophore CytoCy5S. Bacterial-mediated probe activation allowed for non-invasive fluorescence imaging of in vivo bacteria in models of infection and cancer. Chapter 3 extends the concept of using native bacterial enzymes to activate a novel luminescent, NTR activated probe. The use of luminescence based imaging improved the sensitivity of the system and provides researchers with a more accessible modality for preclinical imaging. It also represents an improvement over existing caged luciferin probe systems described to date. Chapter 4 focuses on the employment of endogenous bacterial enzymes for use in a therapeutic setting. Native bacterial enzymatic activity (including NTR enzymes) was shown to be capable of activating multiple prodrugs, in isolation and in combination, and eliciting therapeutic responses in murine models of cancer. Overall, the data presented in this thesis advance the fields of bacterial therapy and imaging and introduce novel strategies for disease diagnosis and treatment. These preclinical studies demonstrate potential for clinical translation in multiple fields of research and medicine.

An Infection-Responsive Approach to Reduce Bacterial Adhesion in Urinary Biomaterials

Infection is an inevitable consequence of chronic urinary catheterisation, with associated problems of recurrent catheter encrustation and blockage experienced by approximately 50% of all long-term catheterised patients. In this work we have exploited, for the first time, the reported pathogen-induced elevation of urine pH as a trigger for ‘intelligent’ antimicrobial release from novel hydrogel drug delivery systems of 2-hydroxyethyl methacrylate and vinyl-functionalised nalidixic acid derivatives, developed as candidate infection-resistant urinary catheter coatings. Demonstrating up to 20-fold faster rates of drug release at pH 10, representing infected urine pH, than at pH 7, and achieving reductions of up to 96.5% in in vitro bacterial adherence, our paradigm of pH-responsive drug delivery, which requires no external manipulation, therefore represents a promising development towards the prevention of catheter-associated urinary tract infections (CAUTIs) in vivo.

Rôle de la conformation des glycoprotéines de l’enveloppe du VIH-1 dans la réponse cytotoxique cellulaire dépendante des anticorps et impact des protéines virales Nef et Vpu

Alors que d’énormes efforts sont mis de l’avant pour mettre en place des stratégies thérapeutiques contre l’infection au VIH-1, il est nécessaire de mieux cerner les déterminants viraux qui aideront à l’efficacité de celles-ci. En ce sens, une volumineuse littérature scientifique suggère que les anticorps contre le VIH-1 possédant une capacité à induire une réponse effectrice dépendante de leur portion Fc puissent jouer un rôle important dans la prévention de l’infection et dans la progression de la maladie. Cependant, peu d’information est disponible concernant les déterminants reconnus par ces anticorps et comment le virus s’en protège. Le but des travaux présentés dans cette thèse est donc d’élucider les mécanismes viraux contrôlant la reconnaissance des cellules infectées par ces anticorps capables d’induire une réponse effectrice. De par les corrélats de protection identifiés au cours de l’essai vaccinal RV144, les travaux présentés ici se concentrent sur la réponse cytotoxique dépendante des anticorps (ADCC), puisqu’il s’agit d’une réponse effectrice suggérée pour avoir joué un rôle dans la protection observée dans le RV144, seul essai vaccinal anti-VIH à avoir démontré un certain degré de protection. De plus, plusieurs anticorps capables d’induire cette réponse contre le VIH sont connus pour reconnaître les glycoprotéines de surface du virus (Env) dans une conformation dite ouverte, c’est-à-dire la conformation adoptée lors de la liaison d’Env avec son récepteur CD4 (épitopes CD4i). Nous avons mis au point deux techniques in vitro permettant d’étudier ces changements de conformation ainsi que leur impact sur la réponse ADCC. Les techniques mises au point, un ÉLISA sur base cellulaire pour mesurer les changements de conformation d’Env ainsi que la mesure de la réponse ADCC par cytométrie en flux, nous ont permis de démontrer comment le virus empêche l’exposition des épitopes d’Env CD4i. L’activité simultanée des protéines accessoires virales Nef et Vpu sur le retrait du récepteur CD4 de la surface des cellules infectées et l’inhibition du facteur de restriction Tétherine / BST-2 par Vpu contrôlent à la fois les niveaux d’Env et de CD4 à la surface cellulaire et donc modulent l’interaction Env-CD4 et ultimement la susceptibilité à la réponse ADCC contre les épitopes CD4i reconnus par des anticorps hautement prévalents lors de l’infection au VIH. Également, nous démontrons comment de petits composés mimant la liaison de CD4 sur Env sont capables de forcer l’exposition des épitopes CD4i, même en présence des protéines Nef et Vpu, et donc d’augmenter la susceptibilité des cellules infectées à la réponse ADCC. Une autre découverte présentée ici est la démonstration que la portion soluble d’Env produite par les cellules infectées peut interagir avec le récepteur CD4 des cellules non-infectées avoisinantes et induire leur reconnaissance et élimination par la réponse ADCC contre Env. Somme toute, la modulation de la réponse ADCC par l’interaction Env–CD4 représente un important pilier de la relation hôte – pathogène du VIH-1 de la perspective des réponses Fc-dépendantes. Les travaux présentés dans cette thèse ont le potentiel d’être utilisés dans l’élaboration de nouvelles stratégies antivirales tout en élargissant les connaissances fondamentales de cette interaction hôte – pathogène.

Evaluating the efficiency of community-based HIV testing and counseling strategies in sub-Saharan Africa

Thesis (Ph.D.)--University of Washington, 2016-08

Dealing with flood damages: will prevention, mitigation, and ex post compensation provide for a resilient triangle?

There is a wealth of literature on the design of ex post compensation mechanisms for natural disasters. However, more research needs to be done on the manner in which these mechanisms could steer citizens toward adopting individual-level preventive and protection measures in the face of flood risks. We have provided a comparative legal analysis of the financial compensation mechanisms following floods, be it through insurance, public funds, or a combination of both, with an empirical focus on Belgium, the Netherlands, England, and France. Similarities and differences between the methods in which these compensation mechanisms for flood damages enhance resilience were analyzed. The comparative analysis especially focused on the link between the recovery strategy on the one hand and prevention and mitigation strategies on the other. There is great potential within the recovery strategy for promoting preventive action, for example in terms of discouraging citizens from living in high-risk areas, or encouraging the uptake of mitigation measures, such as adaptive building. However, this large potential has yet to be realized, in part because of insufficient consideration and promotion of these connections within existing legal frameworks. We have made recommendations about how the linkages between strategies can be further improved. These recommendations relate to, among others, the promotion of resilient reinstatement through recovery mechanisms and the removal of legal barriers preventing the establishment of link-inducing measures.

Genetic manipulation of Anopheles stephensi immunity to increase plasmodium falciparum salivary gland sporozoite infection levels

Human malaria is responsible for over 700,000 deaths a year. To stay abreast of the threat posed by the parasite, a constant stream of new drugs and vector control methods are required. This study focuses on a vaccine that has the potential to protect against parasite infection, but has been hindered by developmental challenges. In malaria prevention, live, attenuated, aseptic, Plasmodium falciparum sporozoites (PfSPZ) can be administered as a highly protective vaccine. PfSPZ are produced using adult female Anopheles stephensi mosquitoes as bioreactors. Production volume and cost of a PfSPZ vaccine for malaria are expected to be directly correlated with Plasmodium falciparum infection intensity in the salivary glands. The sporogonic development of Plasmodium falciparum in A. stephensi to fully infected salivary gland stage sporozoites is dictated by the activities of several known components of the mosquito’s innate immune system. Here I report on the use of genetic technologies that have been rarely, if ever, used in Anopheles stephensi Sda500 to increase the yield of sporozoites per mosquito and enhance vaccine production. By combining the Gal4/UAS bipartite system with in vivo expression of shRNA gene silencing, activity of the IMD signaling pathway downstream effector LRIM1, an antagonist to Plasmodium development, was reduced in the midgut, fat body, and salivary glands of A. stephensi. In infection studies using P. berghei and P. falciparum these transgenic mosquitoes consistently produced significantly more salivary gland stage sporozoites than wildtype controls, with increases in P. falciparum ranging from 2.5 to 10 fold. Using Plasmodium infection assays and qRT-PCR, two novel findings were identified. First, it was shown that 14 days post Plasmodium infection, transcript abundance of the IMD immune effector genes LRIM1, TEP1 and APL1c are elevated, in the salivary glands of A. stephensi, suggesting the salivary glands may play a role in post midgut defense against the parasite. Second, a non-pathogenic IMD signaling pathway response was observed which could suggest an alternative pathway for IMD activation. The information gained from these studies has significantly increased our knowledge of Plasmodium defense in A. stephensi and moreover could significantly improve vaccine production.