Statistical and econometric analysis of the treatment of HIV/AIDS

The epidemic of HIV/AIDS in the United States is constantly changing and evolving, starting from patient zero to now an estimated 650,000 to 900,000 Americans infected. The nature and course of HIV changed dramatically with the introduction of antiretrovirals. This discourse examines many different facets of HIV from the beginning where there wasn't any treatment for HIV until the present era of highly active antiretroviral therapy (HAART). By utilizing statistical analysis of clinical data, this paper examines where we were, where we are and projections as to where treatment of HIV/AIDS is headed.

Chapter Two describes the datasets that were used for the analyses. The primary database utilized was collected by myself from an outpatient HIV clinic. The data included dates from 1984 until the present. The second database was from the Multicenter AIDS Cohort Study (MACS) public dataset. The data from the MACS cover the time between 1984 and October 1992. Comparisons are made between both datasets.

Chapter Three discusses where we were. Before the first anti-HIV drugs (called antiretrovirals) were approved, there was no treatment to slow the progression of HIV. The first generation of antiretrovirals, reverse transcriptase inhibitors such as AZT (zidovudine), DDI (didanosine), DDC (zalcitabine), and D4T (stavudine) provided the first treatment for HIV. The first clinical trials showed that these antiretrovirals had a significant impact on increasing patient survival. The trials also showed that patients on these drugs had increased CD4+ T cell counts. Chapter Three examines the distributions of CD4 T cell counts. The results show that the estimated distributions of CD4 T cell counts are distinctly non-Gaussian. Thus distributional assumptions regarding CD4 T cell counts must be taken, into account when performing analyses with this marker. The results also show the estimated CD4 T cell distributions for each disease stage: asymptomatic, symptomatic and AIDS are non-Gaussian. Interestingly, the distribution of CD4 T cell counts for the asymptomatic period is significantly below that of the CD4 T cell distribution for the uninfected population suggesting that even in patients with no outward symptoms of HIV infection, there exists high levels of immunosuppression.

Chapter Four discusses where we are at present. HIV quickly grew resistant to reverse transcriptase inhibitors which were given sequentially as mono or dual therapy. As resistance grew, the positive effects of the reverse transcriptase inhibitors on CD4 T cell counts and survival dissipated. As the old era faded a new era characterized by a new class of drugs and new technology changed the way that we treat HIV-infected patients. Viral load assays were able to quantify the levels of HIV RNA in the blood. By quantifying the viral load, one now had a faster, more direct way to test antiretroviral regimen efficacy. Protease inhibitors, which attacked a different region of HIV than reverse transcriptase inhibitors, when used in combination with other antiretroviral agents were found to dramatically and significantly reduce the HIV RNA levels in the blood. Patients also experienced significant increases in CD4 T cell counts. For the first time in the epidemic, there was hope. It was hypothesized that with HAART, viral levels could be kept so low that the immune system as measured by CD4 T cell counts would be able to recover. If these viral levels could be kept low enough, it would be possible for the immune system to eradicate the virus. The hypothesis of immune reconstitution, that is bringing CD4 T cell counts up to levels seen in uninfected patients, is tested in Chapter Four. It was found that for these patients, there was not enough of a CD4 T cell increase to be consistent with the hypothesis of immune reconstitution.

In Chapter Five, the effectiveness of long-term HAART is analyzed. Survival analysis was conducted on 213 patients on long-term HAART. The primary endpoint was presence of an AIDS defining illness. A high level of clinical failure, or progression to an endpoint, was found.

Chapter Six yields insights into where we are going. New technology such as viral genotypic testing, that looks at the genetic structure of HIV and determines where mutations have occurred, has shown that HIV is capable of producing resistance mutations that confer multiple drug resistance. This section looks at resistance issues and speculates, ceterus parabis, where the state of HIV is going. This section first addresses viral genotype and the correlates of viral load and disease progression. A second analysis looks at patients who have failed their primary attempts at HAART and subsequent salvage therapy. It was found that salvage regimens, efforts to control viral replication through the administration of different combinations of antiretrovirals, were not effective in 90 percent of the population in controlling viral replication. Thus, primary attempts at therapy offer the best change of viral suppression and delay of disease progression. Documentation of transmission of drug-resistant virus suggests that the public health crisis of HIV is far from over. Drug resistant HIV can sustain the epidemic and hamper our efforts to treat HIV infection. The data presented suggest that the decrease in the morbidity and mortality due to HIV/AIDS is transient. Deaths due to HIV will increase and public health officials must prepare for this eventuality unless new treatments become available. These results also underscore the importance of the vaccine effort.

The final chapter looks at the economic issues related to HIV. The direct and indirect costs of treating HIV/AIDS are very high. For the first time in the epidemic, there exists treatment that can actually slow disease progression. The direct costs for HAART are estimated. It is estimated that the direct lifetime costs for treating each HIV infected patient with HAART is between $353,000 to $598,000 depending on how long HAART prolongs life. If one looks at the incremental cost per year of life saved it is only $101,000. This is comparable with the incremental costs per year of life saved from coronary artery bypass surgery.

Policy makers need to be aware that although HAART can delay disease progression, it is not a cure and HIV is not over. The results presented here suggest that the decreases in the morbidity and mortality due to HIV are transient. Policymakers need to be prepared for the eventual increase in AIDS incidence and mortality. Costs associated with HIV/AIDS are also projected to increase. The cost savings seen recently have been from the dramatic decreases in the incidence of AIDS defining opportunistic infections. As patients who have been on HAART the longest start to progress to AIDS, policymakers and insurance companies will find that the cost of treating HIV/AIDS will increase.

Avaliação regional da contaminação por hidrocarbonetos policíclicos aromáticos (HPAs) na região costeira do sudeste do Brasil usando mexilhões (Perna perna Linneaus 1758) como biomonitores

O objetivo do presente trabalho foi avaliar a presença e a distribuição de hidrocarbonetos policíclicos aromáticos (HPAs) em mexilhões coletados em 23 estações, divididas em três regiões: (i) cultivos localizados no Estado do Rio de Janeiro (7 estações) e em Ubatuba/SP (1 estação); (ii) áreas costeiras no Estado do Rio de Janeiro (7 estações) e (iii) na Baía de Guanabara/RJ (8 estações). Os HPAs foram determinados em triplicata de cada estação, sendo cada réplica formada por uma média de 10 indivíduos, através de cromatografia em fase gasosa acoplada a espectrometria de massas (GC/MS), totalizando 38 compostos entre parentais e alquilados. A concentração média do total de HPAs nos cultivos, excluindo o cultivo de Mombaça (Ilha Grande), foi de 24,7 22,3 ng g-1, para as áreas costeiras foi de 89,7 25,8 ng g-1 e para a Baía de Guanabara, 760,9 456,3 ng g-1. Esses resultados indicam que os cultivos (exceto Mombaça) e as áreas costeiras selecionadas apresentam baixos níveis de contaminação. Já na Baía de Guanabara, os resultados foram comparáveis a dados pretéritos e confirmam o estado de degradação ambiental da baía. Na amostra coletada no cultivo de Mombaça, a alta concentração do total de HPAs (584 ng g-1) e a predominância de compostos alquilados sobre parentais sugerem contaminação relativamente alta por hidrocarbonetos petrogênicos. A análise de agrupamento, considerando o total de HPAs, confirmou a separação entre as três áreas coletadas, mas com algumas exceções: (i) o cultivo de Mombaça assemelha-se ao grupo da Baía de Guanabara; (ii) a estação da Praia Vermelha, na saída da Baía de Guanabara, se assemelha com áreas costeiras fora da baía; (iii) as estações Ilha Redonda, Ilha Comprida e Pontal, distantes mais de 5 km da costa, se agruparam com os cultivos. Somente nas amostras da Baía de Guanabara foi possível avaliar a origem dos HPAs através da análise de componentes principais (PCA). A maioria das amostras da baía apresenta contaminação por fontes mistas de hidrocarbonetos, e apenas na praia Vermelha o aporte pirolítico é mais significativo. Por fim, ressalta-se que os níveis de HPAs nos mexilhões das três áreas ficaram abaixo de valores de referência exigidos internacionalmente para o consumo humano. No entanto, é necessário uma análise de risco específica para melhor compreender a qualidade do mexilhão para consumo humano, particularmente os da Baía de Guanabara.

瓦级双包层光纤超荧光光源的实验研究

采用大功率半导体激光器抽运25m掺Yb双包层光纤，在单程装置中，前向(SPF)和后向(SPB)分别获得了1．46w和1．82w最大超荧光功率，斜度效率分别为23．4％0和29．2％，3dB带宽最大为11nm。采用特定范围波长双色镜作为前腔镜，形成双程前向(DPF)装置，获得最大超荧光输出功率2．12W，此时斜度效率为43．2％，中心波长在1070nm，输出光谱平坦性较好，3dB带宽从单程的11nm提高到42nm。

Dos inscripciones funerarias y una estela oikomorfa en Oña (Burgos)

Edición de dos inscripciones inéditas de Oña (Burgos) y una estela oikomorfa de Poza de la Sal(Burgos)

Petrogênese das rochas máficas alcalinas do litoral entre São Sebastião (SP) e Parati (RJ)

Lamprófiros e diabásios alcalinos afloram no litoral dos estados de São Paulo e Rio de Janeiro e integram o Enxame de Diques da Serra do Mar (EDSM). Essas rochas ocorrem sob a forma de diques e intrudem o Orógeno Ribeira, de idade Neoproterozóica/Cambro-Ordoviciana, inserindo-se no contexto geodinâmico de abertura do Oceano Atlântico Sul durante o Cretáceo Superior. Essas intrusões são subverticais e orientam-se preferencialmente a NE-SW, seguindo a estruturação das rochas encaixantes. Os lamprófiros são classificados como monchiquitos e camptonitos e exibem, respectivamente, textura hipocristalina e holocristalina. Apresentam também textura panidiomórfica, fenocristais de clinopiroxênio e olivina, imersos em matriz formada essencialmente por esses mesmos minerais, além de biotita, kaersutita e minerais opacos. O camptonito apresenta ainda plagioclásio na matriz. Os diabásios alcalinos são hipocristalinos a holocristalinos, equigranulares a inequigranulares, com fenocristais de olivina e/ou clinopiroxênio e/ou plagioclásio, em uma matriz composta essencialmente por esses minerais. As rochas estudadas caracterizam séries alcalinas miaskíticas, com os lamprófiros sendo tanto sódicos, potássicos e ultrapotássicos e os diabásios alcalinos como predominantemente sódicos. Modelagens petrogenéticas envolvendo possíveis processos evolutivos mostram que é improvável que os lamprófiros sejam cogenéticos por processos evolutivos envolvendo tanto cristalização fracionada, com ou sem assimilação concomitante, quanto hibridização. O mesmo ocorre para os diabásios alcalinos. A discriminação de fontes mantélicas foi feita com base nos teores de elementos traços de amostras representativas de líquidos parentais e indica que esse magmatismo alcalino está relacionado a fontes lherzolíticas com fusão parcial na zona de estabilidade do espinélio, isto é, a poucas profundidades. Os dados litogeoquímicos e isotópicos do sistema Sr-Nd das rochas estudadas sugerem tanto o envolvimento de fontes férteis, associadas ao manto sublitosférico, quanto de fontes enriquecidas, relacionadas ao manto litosférico subcontinental. Modelagens de mistura binária revelam que a petrogênese dos lamprófiros e diabásios alcalinos envolveu uma grande participação de um componente fértil misturado com contribuições menores de um componente enriquecido. Idades TDM (760-557 Ma) obtidas sugerem remobilização do manto litosférico no Neoproterozóico, talvez relacionadas à subducção da Placa São Francisco preteritamente à colisão do Orógeno Ribeira. Altas razões CaO/Al2O3 para os líquidos lamprofíricos menos evoluídos, altos teores de Zr, correlações negativas Zr/Hf e Ti/Eu e associação com carbonatitos indicam condições metassomáticas de alto CO2/H2O. Em escala local, modelos geodinâmicos baseados na astenosfera não isotérmica parecem mais aplicáveis. No entanto, modelos geodinâmicos baseados na astenosfera isotérmica (com o envolvimento de plumas) parecem mais indicados num contexto regional, considerando-se outras províncias alcalinas contemporâneas e correlatas.

HfO2 膜料中的杂质对薄膜损伤及性能的影响

By analysis of impurity elements in HfO2 coating material, the influence of main impurity elements on the characteristic of coatings were studied. The results indicate that the metal elements and absorptive dielectric elements damage the HfO2 coatings. The more the Zr element content is, the more the absorption is for the coatings in ultraviolet wave. The negative ion element will become the gas source center and form an ejection in the process of evaporation of coating material, so decrease the damage threshold of the coatings.

SiO_2薄膜折射率的准确拟合分析

精确的光学常数对于设计和制备高品质的光学薄膜非常重要,尤其是那些光学性能对折射率变化敏感的薄膜。SiO_2是一种常用的低折射率材料,因与常用基底折射率相近使其准确拟合有一定难度。实验通过离子束溅射制备了SiO_2单层膜。考虑测量时的误差和基底折射率的影响,采用透射率包络和反射率包络得到了SiO_2的折射率,并用所得折射率进行反演来对这两种途径在实际测量拟合过程中的准确性进行比对。分析表明,剩余反射率在实际的测量过程中误差更小,直接用测量镀膜前后基片的剩余反射率值可以更简便更准确地得到SiO_2的折射率,能达到10~(-2)的精度。

Ethnography as a linking method between psychology and sociology: research design

World Conference on Psychology and Sociology 2012