Health Insurance, Employment, and the Human Genome: Genetic Discrimination and Biobanks in the United States

Does genetic information warrant special legal protection, and if so how should it be protected? This essay examines the most recent (and indeed only) significant effort by the US government to prohibit genetic discrimination, the Genetic Information Nondiscrimination Act (GINA). We argue that the legislation is unlikely to have the positive impact sought by advocates of genetic privacy and proponents of biobanks. In part, GINA disappoints because it does too little. Hailed by its promoters as “the first civil rights act of the 21st century,” GINA’s reach is in fact quite modest and its grasp even more so. But GINA also fails by trying to do too much, tying the hands of insurers and employers in ways that may fail to serve the interests of individuals or society more generally. In short, if genetic discrimination is a problem that needs to be solved, GINA is not the solution. Instead, the Act creates a number of new and possibly intractable problems that may be more troublesome than what it originally set out to resolve

Institutional reform and FDI decision in transition economies: a qualitative study of Syria

The article considers the impact of institutional reform on the decision of foreign enterprises and foreign entrepreneurs to directly invest in the transition economy of Syria. It responds to the calls for more open research design that can go beyond the borders of the quantitative findings of previous econometric research by adopting a qualitative research strategy. The results reveal that institutional reforms enhanced Syria’s attractiveness to foreign direct investment. Institutional barriers proved to be less daunting to foreign investors whose backgrounds were culturally similar to that of Syria and/or already had experience in Syria or in a similar type of economy. The impact of background similarity and previous experience in similar contexts appeared to be less important when the foreign investor was a multinational enterprise than for individual entrepreneur. Moreover, these factors also appeared to be less important for large enterprises compared to small enterprises

Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel

Capacity and Autonomy : An Exploration of Fukuyama’s Governance Hypothesis

Peer reviewe

Fast approximate hierarchical clustering using similarity heuristics

© 2008 Kull and Vilo; licensee BioMed Central Ltd

Risco de câncer de pulmão, laringe e esôfago atribuível ao fumo

OBJECTIVE:Lung, laryngeal and esophageal cancers have smoking as one of their main risk factors. The objective of this study was to evaluate the population attributed risk (PAR) of smoking for these forms of cancer. METHODS: The study was based in three case-control studies conducted in medium size cities in Brazil. Incident cases of lung cancer, laryngeal cancer and esophageal cancer seen at a hospital setting and diagnosed through biopsy were analyzed; controls were hospitalized patients with another diagnoses. Smoking was the exposure factor measured at three levels: non-smokers, former smokers and smokers, which were defined using a questionnaire applied by trained interviewers. For effect measure, odds ratio was used and the populational attributed risk for smoking was then calculated for a 95% CI. RESULTS: A total of 122 lung cancer cases and 244 controls, 50 cases of laryngeal cancer and 48 cases of esophageal cancer, and 96 controls for both of them were studied. The prevalence of smoking exposure was 34%, which is the overall prevalence of smoking in this city's adult population. Odds ratios (OR) for the PAR analysis were the adjusted OR for confounding variables from each study. Lung cancer PAR was 63% (95% IC, 0.58-0.68) for former smokers and 71% (95%IC, 0.65-0.77) for smokers. Larynx cancer PAR was 74% (95% IC, 0.70-0.78) and 86% (95%IC, 0.81-0.85) for former smokers and smokers, respectively. Esophageal cancer PAR was 54% (95%IC, 0.46-0.62) for smokers. CONCLUSION: Smoking is an avoidable risk factor and smoking cessation could be responsible for significant reductions in the incidence of these three forms of cancer.OBJETIVO: Os tipos de câncer de pulmão, laringe e esôfago têm como um de seus principais fatores de risco o fumo. O objetivo do estudo foi avaliar o risco populacional atribuível ao fumo nesses tipos de câncer. MÉTODOS: A pesquisa baseou-se em três estudos de caso-controle em cidade de médio porte do Brasil. Analisaram-se casos incidentes hospitalares de câncer de pulmão, de laringe e de esôfago diagnosticados por biópsias; os controles foram pacientes hospitalizados por outros motivos, sem ser câncer ou doenças altamente relacionadas ao fumo. O fator de exposição foi o tabagismo medido em três níveis: não-fumantes, ex-fumantes e fumantes atuais, definidos por meio de questionários aplicados por entrevistadores treinados. Para a medida de efeito, foi utilizado o odds ratio obtendo-se, dessa forma, o "risco populacional atribuível" ao fumo com IC de 95%. RESULTADOS: Foram estudados 122 casos e 244 controles de câncer de pulmão, 50 casos de câncer de laringe e 48 casos de câncer de esôfago, com um grupo de 96 controles comum a ambos. A prevalência da exposição ao fumo utilizada para a análise foi de 34%, que corresponde à prevalência de fumo na população adulta da cidade. Os odds ratios para o cálculo do risco populacional atribuível foram obtidos por análises ajustadas para os fatores de confusão de cada um dos estudos. Para ex-fumantes com câncer de pulmão, o risco populacional atribuível foi de 63% (IC95%, 0,58-0,68) e, para fumantes, de 71% (IC95%, 0,65-0,77). Para câncer de laringe, o RPA foi de 74% (IC95%, 0,70-0,78) para ex-fumantes e de 86% (IC95%, 0,81-0,85) para fumantes. O câncer de esôfago mostrou um risco de 54% (IC95%, 0,46-0,62) para fumantes. CONCLUSÃO: Conclui-se que o fumo é um importante fator de risco e que a cessação do mesmo contribuiria para reduções significativas na incidência de câncer nesses três sítios

Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional 1H-MRS study

Proton magnetic resonance spectroscopy (1H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS (31P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional 1H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1–0.2 μmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients

Construction and Modelling of an Inducible Positive Feedback Loop Stably Integrated in a Mammalian Cell-Line

Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the “switch off” times, as comparared to the nonautoregulatated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour