ADVANCED ISLANDING DETECTION METHODS FOR SINGLE PHASE GRID CONNECTED PV INVERTERS

Due to the growing concerns associated with fossil fuels, emphasis has been placed on clean and sustainable energy generation. This has resulted in the increase in Photovoltaics (PV) units being integrated into the utility system. The integration of PV units has raised some concerns for utility power systems, including the consequences of failing to detect islanding. Numerous methods for islanding detection have been introduced in literature. They can be categorized into local methods and remote methods. The local methods are categorically divided into passive and active methods. Active methods generally have smaller Non-Detection Zone (NDZ) but the injecting disturbances will slightly degrade the power quality and reliability of the power system. Slip Mode Frequency Shift Islanding Detection Method (SMS IDM) is an active method that uses positive feedback for islanding detection. In this method, the phase angle of the converter is controlled to have a sinusoidal function of the deviation of the Point of Common Coupling (PCC) voltage frequency from the nominal grid frequency. This method has a non-detection zone which means it fails to detect islanding for specific local load conditions. If the SMS IDM employs a different function other than the sinusoidal function for drifting the phase angle of the inverter, its non-detection zone could be smaller. In addition, Advanced Slip Mode Frequency Shift Islanding Detection Method (Advanced SMS IDM), which has been introduced in this thesis, eliminates the non-detection zone of the SMS IDM. In this method the parameters of SMS IDM change based on the local load impedance value. Moreover, the stability of the system is investigated by developing the dynamical equations of the system for two operation modes; grid connected and islanded mode. It is mathematically proven that for some loading conditions the nominal frequency is an unstable point and the operation frequency slides to another stable point, while for other loading conditions the nominal frequency is the only stable point of the system upon islanding occurring. Simulation and experimental results show the accuracy of the proposed methods in detection of islanding and verify the validity of the mathematical analysis.

Pedagogia de esporte : aspectos motriz de aprendizagem em hoquei em patins, crianças de oito a dez anos

Universidade Estadual de Campinas. Faculdade de Educação Física

Ensino, aprendizagem e avaliação no Ensino Superior: Perspetivas e práticas

Tese de Doutoramento em Ciências da Educação - Especialidade de Desenvolvimento Curricular

Gender differences in HIV progression to AIDS and death in industrialized countries: slower disease progression following HIV seroconversion in women.

To evaluate sex differences in human immunodeficiency virus (HIV) disease progression before (pre-1997) and after (1997-2006) introduction of highly active antiretroviral therapy, the authors used data from a collaboration of 23 HIV seroconverter cohort studies from Europe, Australia, and Canada restricted to the 6,923 seroconverters infected through injecting drug use and sex between men and women. Within a competing risk framework, they used Cox proportional hazards models allowing for late entry to evaluate sex differences in time from HIV seroconversion to death, to acquired immunodeficiency syndrome (AIDS), and to each first AIDS-defining disease and death without AIDS. While no significant sex differences were found before 1997, from 1997 onward, women had a lower risk of AIDS (adjusted cumulative relative risk (aCRR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and death (adjusted hazard ratio = 0.68, 95% CI: 0.56, 0.82) than men did. Compared with men, women also had lower risks of AIDS dementia complex (aCRR = 0.23, 95% CI: 0.07, 0.74), tuberculosis (aCRR = 0.60, 95% CI: 0.39, 0.92), Kaposi's sarcoma (aCRR = 0.27, 95% CI: 0.07, 0.99), lymphomas (aCRR = 0.47, 95% CI: 0.23, 0.96), and death without AIDS (aCRR = 0.74, 95% CI: 0.56, 0.98). Sex differences in HIV disease progression have become larger and statistically significant in the era of highly active antiretroviral therapy, supporting a stronger impact of health interventions among women.

Antiretroviral treatment during pregnancy.

OBJECTIVE: Virologic failure of HIV-positive patients is of special concern during pregnancy. We compared virologic failure and the frequency of treatment changes in pregnant and non-pregnant women of the Swiss HIV Cohort Study. METHODS: Using data on 372 pregnancies in 324 women we describe antiretroviral therapy during pregnancy. Pregnant women on HAART at conception (n = 131) were matched to 228 non-pregnant women (interindividual comparison) and to a time period of equal length before and after pregnancy (intraindividual comparison). Women starting HAART during pregnancy (n = 145) were compared with 578 non-pregnant women starting HAART. FINDINGS: The median age at conception was 31 years, 16% (n = 50) were infected through injecting drug use and the median CD4 cell count was 489 cells/microl. In the majority of pregnancies (n = 220, 59%), women had started ART before conception. When ART was started during pregnancy (n = 145, 39%), it was mainly during the second trimester (n = 100, 69%). Two thirds (n = 26) of 35 women starting in the third trimester were diagnosed with HIV during pregnancy. The risk of virologic failure tended to be lower in pregnant than in non-pregnant women [adjusted odds ratio 0.52 (95% confidence interval 0.25-1.09, P = 0.08)], but was similar in the intraindividual comparison (adjusted odds ratio 1.04, 95% confidence interval 0.48-2.28). Women starting HAART during pregnancy changed the treatment less often than non-pregnant women. CONCLUSION: Despite the physiological changes occurring during pregnancy, HIV infected pregnant women are not at higher risk of virologic failure.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study.

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

Interplay between T cell receptor binding kinetics and the level of cognate peptide presented by major histocompatibility complexes governs CD8+ T cell responsiveness.

Through a rational design approach, we generated a panel of HLA-A*0201/NY-ESO-1(157-165)-specific T cell receptors (TCR) with increasing affinities of up to 150-fold from the wild-type TCR. Using these TCR variants which extend just beyond the natural affinity range, along with an extreme supraphysiologic one having 1400-fold enhanced affinity, and a low-binding one, we sought to determine the effect of TCR binding properties along with cognate peptide concentration on CD8(+) T cell responsiveness. Major histocompatibility complexes (MHC) expressed on the surface of various antigen presenting cells were peptide-pulsed and used to stimulate human CD8(+) T cells expressing the different TCR via lentiviral transduction. At intermediate peptide concentration we measured maximum cytokine/chemokine secretion, cytotoxicity, and Ca(2+) flux for CD8(+) T cells expressing TCR within a dissociation constant (K(D)) range of ∼1-5 μM. Under these same conditions there was a gradual attenuation in activity for supraphysiologic affinity TCR with K(D) < ∼1 μM, irrespective of CD8 co-engagement and of half-life (t(1/2) = ln 2/k(off)) values. With increased peptide concentration, however, the activity levels of CD8(+) T cells expressing supraphysiologic affinity TCR were gradually restored. Together our data support the productive hit rate model of T cell activation arguing that it is not the absolute number of TCR/pMHC complexes formed at equilibrium, but rather their productive turnover, that controls levels of biological activity. Our findings have important implications for various immunotherapies under development such as adoptive cell transfer of TCR-engineered CD8(+) T cells, as well as for peptide vaccination strategies.

Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid.

OBJECTIVES: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments with higher central nervous system penetration-effectiveness (CPE) achieve better CSF viral suppression. METHODS: Viral loads (VLs) and drug concentrations of lopinavir, atazanavir, and efavirenz were measured in plasma and CSF. The CPE was calculated using 2 different methods. RESULTS: The authors analyzed 87 CSF samples of 60 patients. In 4 CSF samples, HIV-1 RNA was detectable with 43-82 copies per milliliter. Median CPE in patients with detectable CSF VL was significantly lower compared with individuals with undetectable VL: CPE of 1.0 (range, 1.0-1.5) versus 2.3 (range, 1.0-3.5) using the method of 2008 (P = 0.011) and CPE of 6 (range, 6-8) versus 8 (range, 5-12) using the method of 2010 (P = 0.022). The extrapolated CSF trough levels for atazanavir (n = 12) were clearly above the 50% inhibitory concentration (IC50) in only 25% of samples; both patients on atazanavir/ritonavir with detectable CSF HIV-1 RNA had trough levels in the range of the presumed IC50. The extrapolated CSF trough level for lopinavir (n = 42) and efavirenz (n = 18) were above the IC50 in 98% and 78%, respectively, of samples, including the patients with detectable CSF HIV-1 RNA. CONCLUSIONS: This study suggests that treatment regimens with high intracerebral efficacy reflected by a high CPE score are essential to achieve CSF HIV-1 RNA suppression. The CPE score including all drug components was a better predictor for treatment failure in the CSF than the sole concentrations of protease inhibitor or nonnucleoside reverse transcriptase inhibitor in plasma or CSF.

Small dense lipoproteins, apolipoprotein B, and risk of coronary events in HIV-infected patients on antiretroviral therapy: the Swiss HIV Cohort Study.

OBJECTIVES: HIV infection and exposure to certain antiretroviral drugs is associated with dyslipidemia and increased risk for coronary events. Whether this risk is mediated by highly atherogenic lipoproteins is unclear. We investigated the association of highly atherogenic small dense low-density lipoproteins (LDLs) and apolipoprotein B and coronary events in HIV-infected individuals receiving antiretroviral therapy. METHODS: We conducted a case-control study nested into the Swiss HIV Cohort Study to investigate the association of small dense LDL and apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients with a first coronary event (19 fatal and 79 nonfatal coronary events with 53 definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses) and 393 treated controls matched for age, gender, and smoking status. Lipids were measured by ultracentrifugation. RESULTS: In models including cholesterol, triglycerides, high-density lipoprotein cholesterol, blood pressure, central obesity, diabetes, and family history, there was an independent association between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10) for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both models, blood pressure and HIV viral load was independently associated with the odds for coronary events. CONCLUSIONS: HIV-infected patients receiving antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at increased risk for coronary events as are patients without sustained HIV suppression.

Implementation of raltegravir in routine clinical practice: selection criteria for choosing this drug, virologic response rates, and characteristics of failures.

BACKGROUND: Raltegravir (RAL) achieved remarkable virologic suppression rates in randomized-clinical trials, but today efficacy data and factors for treatment failures in a routine clinical care setting are limited. METHODS: First, factors associated with a switch to RAL were identified with a logistic regression including patients from the Swiss HIV Cohort Study with a history of 3 class failure (n = 423). Second, predictors for virologic outcome were identified in an intent-to-treat analysis including all patients who received RAL. Last observation carried forward imputation was used to determine week 24 response rate (HIV-1 RNA >or= 50 copies/mL). RESULTS: The predominant factor associated with a switch to RAL in patients with suppressed baseline RNA was a regimen containing enfuvirtide [odds ratio 41.9 (95% confidence interval: 11.6-151.6)]. Efficacy analysis showed an overall response rate of 80.9% (152/188), whereas 71.8% (84/117) and 95.8% (68/71) showed viral suppression when stratified for detectable and undetectable RNA at baseline, respectively. Overall CD4 cell counts increased significantly by 42 cells/microL (P < 0.001). Characteristics of failures were a genotypic sensitivity score of the background regimen <or=1, very low RAL plasma concentrations, poor adherence, and high viral load at baseline. CONCLUSIONS: Virologic suppression rates in our routine clinical care setting were promising and comparable with data from previously published randomized-controlled trials.

Current state of vaccine therapies in non-small-cell lung cancer.

A large variety of cancer vaccines have undergone extensive testing in early-phase clinical trials. A limited number have also been tested in randomized phase II clinical trials. Encouraging trends toward increased survival in the vaccine arms have been recently observed for 2 vaccine candidates in patients with non-small-cell lung cancer. These have provided the impetus for the initiation of phase III trials in large groups of patients with lung cancer. These vaccines target 2 antigens widely expressed in lung carcinomas: melanoma-associated antigen 3, a cancer testis antigen; and mucin 1, an antigen overexpressed in a largely deglycosylated form in advanced tumors. Therapeutic cancer vaccines aim at inducing strong CD8 and CD4 T-cell responses. The majority of vaccines recently tested in phase I clinical trials show efficacy in terms of induction of specific tumor antigen immunity. However, clinical efficacy remains to be determined but appears limited. Efforts are thus aimed at understanding the basis for this apparent lack of effect on tumors. Two major factors are involved. On one hand, current vaccines are suboptimal. Strong adjuvant agents and appropriate tumor antigens are needed. Moreover, dose, route, and schedule also need optimization. On the other hand, it is now clear that large tumors often present a tolerogenic microenvironment that hampers effective antitumor immunity. The partial understanding of the molecular pathways leading to functional inactivation of T cells at tumor sites has provided new targets for intervention. In this regard, blockade of cytotoxic T-lymphocyte antigen-4 and programmed death-1 with humanized monoclonal antibodies has reached the clinical testing stage. In the future, more potent cancer vaccines will benefit from intense research in antigen discovery and adjuvant agents. Furthermore, it is likely that vaccines need to be combined with compounds that reverse major tolerogenic pathways that are constitutively active at the tumor site. Developing these combined approaches to vaccination in cancer promises new, exciting findings and, at the same time, poses important challenges to academic research institutions and the pharmaceutical industry.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Medical treatment and the good death: an ethical analysis of euthanasia, physician assisted suicide, and the right to die

Frequent advances in medical technologies have brought fonh many innovative treatments that allow medical teams to treal many patients with grave illness and serious trauma who would have died only a few years earlier. These changes have given some patients a second chance at life, but for others. these new treatments have merely prolonged their dying. Instead of dying relatively painlessly, these unfortunate patients often suffer from painful tenninal illnesses or exist in a comatose state that robs them of their dignity, since they cannot survive without advanced and often dehumanizing forms of treatment. Due to many of these concerns, euthanasia has become a central issue in medical ethics. Additionally, the debate is impacted by those who believe that patients have the right make choices about the method and timing of their deaths. Euthanasia is defined as a deliberate act by a physician to hasten the death of a patient, whether through active methods such as an injection of morphine, or through the withdrawal of advanced forms of medical care, for reasons of mercy because of a medical condition that they have. This study explores the question of whether euthanasia is an ethical practice and, as determined by ethical theories and professional codes of ethics, whether the physician is allowed to provide the means to give the patient a path to a "good death," rather than one filled with physical and mental suffering. The paper also asks if there is a relevant moral difference between the active and passive forms of euthanasia and seeks to define requirements to ensure fully voluntary decision making through an evaluation of the factors necessary to produce fully informed consent. Additionally, the proper treatments for patients who suffer from painful terminal illnesses, those who exist in persistent vegetative states and infants born with many diverse medical problems are examined. The ultimate conclusions that are reached in the paper are that euthanasia is an ethical practice in certain specific circumstances for patients who have a very low quality of life due to pain, illness or serious mental deficits as a result of irreversible coma, persistent vegetative state or end-stage clinical dementia. This is defended by the fact that the rights of the patient to determine his or her own fate and to autonomously decide the way that he or she dies are paramount to all other factors in decisions of life and death. There are also circumstances where decisions can be made by health care teams in conjunction with the family to hasten the deaths of incompetent patients when continued existence is clearly not in their best interest, as is the case of infants who are born with serious physical anomalies, who are either 'born dying' or have no prospect for a life that is of a reasonable quality. I have rejected the distinction between active and passive methods of euthanasia and have instead chosen to focus on the intentions of the treating physician and the voluntary nature of the patient's request. When applied in equivalent circumstances, active and passive methods of euthanasia produce the same effects, and if the choice to hasten the death of the patient is ethical, then the use of either method can be accepted. The use of active methods of euthanasia and active forms of withdrawal of life support, such as the removal of a respirator are both conscious decisions to end the life of the patient and both bring death within a short period of time. It is false to maintain a distinction that believes that one is active killing. whereas the other form only allows nature to take it's course. Both are conscious choices to hasten the patient's death and should be evaluated as such. Additionally, through an examination of the Hippocratic Oath, and statements made by the American Medical Association and the American College of physicians, it can be shown that the ideals that the medical profession maintains and the respect for the interests of the patient that it holds allows the physician to give aid to patients who wish to choose death as an alternative to continued suffering. The physician is also allowed to and in some circumstances, is morally required, to help dying patients whether through active or passive forms of euthanasia or through assisted suicide. Euthanasia is a difficult topic to think about, but in the end, we should support the choice that respects the patient's autonomous choice or clear best interest and the respect that we have for their dignity and personal worth.

Desempenho cognitivo em diferentes níveis de escolaridade de adultos e idosos ativos

OBJETIVO: Comparar o desempenho cognitivo em diferentes níveis de escolaridade de indivíduos adultos e idosos praticantes de atividade física. MÉTODOS: Foram avaliados 122 indivíduos sem comprometimento cognitivo, idade entre 46 a 85 anos e escolaridade entre 1 a 15 anos, praticantes de atividade física há mais de 6 meses no Programa de Atividades Físicas e Recreativas para a Terceira Idade. Foi aplicada uma bateria de testes cognitivos para verificar as seguintes variáveis: memória de curto prazo, linguagem, aprendizagem, taxa de esquecimento e funções executivas. RESULTADOS: O teste de Kruskal-Wallis apontou diferenças entre os grupos, com diferentes níveis de escolaridade, apenas para a memória de curto prazo, sendo que o teste de U Mann Whitney demonstra diferença entre o grupo de menor escolaridade (1-4 anos) com o grupo de maior escolaridade (> 12 anos). CONCLUSÃO: Diante disso, sugere-se que adultos e idosos ativos, em diferentes níveis de escolaridade, apresentam um perfil cognitivo semelhante para os seguintes domínios cognitivos: linguagem, aprendizagem, taxa de esquecimento e funções executivas.