A gestão estratégica de pessoas do tribunal de contas do Rio Grande do Sul

Neste presente estudo, objetiva-se identificar como a Gestão Estratégica de Pessoas do Tribunal de Contas do Rio Grande do Sul se articula para resolver e minimizar as dificuldades do órgão, no que diz respeito à implantação e a solução de problemas de gestão de pessoas. Somado a isso, também foi investigado quais são os principais desafios e dificuldades na gestão de pessoas e na aplicação da gestão estratégica de pessoas no serviço público, e como o Tribunal de Contas se articula para superá-los. A administração pública, em diversos países, passou por reformas significativas a partir da década de 1980. Práticas gerenciais da iniciativa privada foram adotadas como referência para transposição para o setor público, visando à geração de maior eficiência e foco em resultado (BRESSER PEREIRA apud FONSECA et al., 2013). Dentre as atividades que deveriam ser modernizadas encontra-se a gestão de recursos humanos (RH), até então voltada, no Governo como um todo, para sua função clássica de registro e controle de custos de funcionários. A sociedade vem exigindo do poder público uma atuação cada vez mais voltada para o alcance de resultados, isto é, além da eficiência tão perseguida pelas organizações nos últimos tempos, atualmente a eficácia e a efetividade da ação governamental são as palavras de ordem. Para tanto, foi elaborado um estudo de caso no Tribunal de Contas do Rio Grande do Sul, mostrando as práticas de gestão estratégica de pessoas implementadas pelo órgão. Assim sendo, o estudo reúne as práticas de gestão estratégica de pessoas, que obtiveram êxito no Tribunal de Contas, assim como as especificidades e os limites que delimitam a implantação desse tipo de estratégias, políticas e ações/

Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA

Human immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of “negatively associated” or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development

Relative resistance of HIV-1 founder viruses to control by interferon-alpha

Background: Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. Results: The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNα2 (22 U/ml) was lower than that for IFNβ (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNα2 and IFNβ, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNα than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. Conclusions: The establishment of systemic HIV-1 infection by relatively IFNα-resistant founder viruses lends strong support to the hypothesis that IFNα plays an important role in the control of HIV-1 replication during the earliest stages of infection, prior to systemic viral spread. These findings suggest that it may be possible to harness the antiviral activity of type 1 IFNs in prophylactic and potentially also therapeutic strategies to combat HIV-1 infection

Intrapatient Escape in the A*0201-Restricted Epitope SLYNTVATL Drives Evolution of Human Immunodeficiency Virus Type 1 at the Population Level

The hypothesis that the intrapatient emergence of cytotoxic T-lymphocyte escape variants contributes to the evolution of human immunodeficiency virus type 1 at the population (interpatient) level was tested using the HLA-A*0201-restricted gag p17 epitope SLYNTVATL. Using a simple experimental design, we investigated the evolutionary processes operating within this epitope among patients while compensating for the confounding influence of intrapatient natural selection. Using this approach, we revealed a pattern of A*0201-driven escape within patients, followed by the sustained transmission of these escape variants among patients irrespective of their HLA type

Examples of likely GT-specific responses using ELISpot analysis.

<p>The two panels (A) and (B) represent GT1-epitopes that elicited responses from GT3-infected subjects. Peptides representing GT1 peptides tested in the original ELISpot screen and in a subsequent ELISpot with the alternative GT3 peptide(s). Original screen result is shown on the front row (grey) and subsequent ELISpot assay on the second row (black; mean SFU/10⁶ PBMCs from duplicates). Each panel represents data from a single subject.</p

Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection▿

Hepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed. We performed full-length viral sequence analysis in 18 patients with chronic HCV subtype 3a infection and assessed genomic viral variability in comparison to other HCV subtypes. Two novel regions of intragenotypic hypervariability within the envelope protein E2, of HCV genotype 3a, were identified. We named these regions HVR495 and HVR575. They consisted of flanking conserved hydrophobic amino acids and central variable residues. A 5-amino-acid insertion found only in genotype 3a and a putative glycosylation site is contained within HVR575. Evolutionary analysis of E2 showed that positively selected sites within genotype 3a infection were largely restricted to HVR1, HVR495, and HVR575. Further analysis of clonal viral populations within single hosts showed that viral variation within HVR495 and HVR575 were subject to intrahost positive selecting forces. Longitudinal analysis of four patients with acute HCV subtype 3a infection sampled at multiple time points showed that positively selected mutations within HVR495 and HVR575 arose early during primary infection. HVR495 and HVR575 were not present in HCV subtypes 1a, 1b, 2a, or 6a. Some variability that was not subject to positive selection was present in subtype 4a HVR575. Further defining the functional significance of these regions may have important implications for genotype 3a E2 virus-receptor interactions and for vaccine studies that aim to induce cross-reactive anti-E2 antibodies

Chronic non-GT1-infected individuals are able to mount T-cell responses to GT1 epitopes.

<p>The SFU/million PBMCs are shown for subjects with known GT1 infection and non-GT1 infection. Although subjects may have responded to more than one peptide covering an epitope, in this figure only the highest response was used.</p

Subject demographics and clinical data.

<p>* information unknown due to limited clinical history or lack of viraemic plasma sample</p><p>^{^} includes a single individual co-infected with GT1 and GT3 strains</p><p>^# predominately IDU and Tattoo</p><p>Subject demographics and clinical data.</p

Breakdown of HLA-specific T-cell targets tested and number eliciting a T-cell response based on an IFN-γ ELISpot assay.

<p>Predicted T-cell targets include published HCV T-cell targets that contain a site associated with a specific HLA allele with the same restriction. Number in bracket indicates number of subjects tested that carry the particular HLA type.</p