22 research outputs found

    Theory of neutrinoless double beta decay

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    Neutrinoless double beta decay, which is a very old and yet elusive process, is reviewed. Its observation will signal that lepton number is not conserved and the neutrinos are Majorana particles. More importantly it is our best hope for determining the absolute neutrino mass scale at the level of a few tens of meV. To achieve the last goal certain hurdles have to be overcome involving particle, nuclear and experimental physics. Nuclear physics is important for extracting the useful information from the data. One must accurately evaluate the relevant nuclear matrix elements, a formidable task. To this end, we review the sophisticated nuclear structure approaches recently been developed, which give confidence that the needed nuclear matrix elements can be reliably calculated. From an experimental point of view it is challenging, since the life times are long and one has to fight against formidable backgrounds. If a signal is found, it will be a tremendous accomplishment. Then, of course, the real task is going to be the extraction of the neutrino mass from the observations. This is not trivial, since current particle models predict the presence of many mechanisms other than the neutrino mass, which may contribute or even dominate this process. We will, in particular, consider the following processes: (i)The neutrino induced, but neutrino mass independent contribution. (ii)Heavy left and/or right handed neutrino mass contributions. (iii)Intermediate scalars (doubly charged etc). (iv)Supersymmetric (SUSY) contributions. We will show that it is possible to disentangle the various mechanisms and unambiguously extract the important neutrino mass scale, if all the signatures of the reaction are searched in a sufficient number of nuclear isotopes.Comment: 104 pages, 6 tables, 25 figures.References added. To appear in ROP (Reports on Progress in Physics), copyright RO

    The 'COmorBidity in Relation to AIDS' (COBRA) cohort: Design, methods and participant characteristics

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    BACKGROUND: Persons living with HIV on combination antiretroviral therapy (cART) may be at increased risk of the development of age-associated non-communicable comorbidities (AANCC) at relatively young age. It has therefore been hypothesised that such individuals, despite effective cART, may be prone to accelerated aging. OBJECTIVE: The COmorBidity in Relation to AIDS (COBRA) cohort study was designed to investigate the potential causal link between HIV and AANCC, amongst others, in a cohort of middle-aged individuals with HIV with sustained viral suppression on cART and otherwise comparable HIV-negative controls. METHODS: Longitudinal cohort study of HIV-positive subjects ≥45 years of age, with sustained HIV suppression on cART recruited from two large European HIV treatment centres and similarly-aged HIV-negative controls recruited from sexual health centres and targeted community groups. Both HIV-positive and HIV-negative subjects were assessed at study entry and again at follow-up after 2 years. RESULTS: Of the 134 HIV-positive individuals with a median (IQR) age of 56 (51, 62) years recruited, 93% were male, 88% of white ethnicity and 86% were men who have sex with men (MSM). Similarly, the 79 HIV-negative subjects had a median (IQR) age of 57 (52, 64) and 92% were male, 97% of white ethnicity and 80% were MSM. CONCLUSIONS: The results from the COBRA study will be a significant resource to understand the link between HIV and AANCC and the pathogenic mechanisms underlying this link. COBRA will inform future development of novel prognostic tools for earlier diagnosis of AANCC and of novel interventions which, as an adjunct to cART, may prevent AANCC

    Do we need universal competence in space

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    В данной статье рассматривается вопрос влияния личностных качеств на профессиональную деятельность. К чему может привести отсутствие компетенций? Какими качествами должен обладать космонавт - испытатель? Проведен анализ трудовых функций космонавта - испытателя, и по этим данным подобраны универсальные компетенции космонавта, находящегося в космосе. Универсальные компетенции - это качества личности, от которых зависит ее успех практически во всех областях профессиональной деятельности.This article discusses the question of the impact of personal qualities on professional activities. What can be due to lack of competencies? What are the qualities of a test cosmonaut? The analysis of the job functions of test - cosmonaut on this data selected generic competence astronaut is in space. Universal jurisdiction is the quality of the person depends on its success in almost all areas of professional activity

    Increased brain-predicted aging in treated HIV disease

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    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machinelearning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 1890 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD 5 brain-predicted brain age 2 chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean +/- SD 2.15 +/- 7.79 years) compared to HIV-negative individuals (20.87 +/- 8.40 years; b = 3.48, p < 0.01). Increased brainPAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging

    Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

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    Background: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. // Methods: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. // Results: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P <.05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P <.05), as well as smaller brain volumes (P <.01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. // Conclusion: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach

    High cellular monocyte activation in people living with human immunodeficiency virus on combination antiretroviral therapy and lifestyle-matched controls is associated with greater inflammation in cerebrospinal fluid

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    Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF

    No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project

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    Background: Despite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology. Methods: We performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models. Results: 123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels. At baseline, PLWH had poorer global cognitive performance (P0.1). Cognitive performance was stable across the study period in both groups. Conclusions: Our finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls

    Do people living with HIV experience greater age advancement than their HIV-negative counterparts?

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    OBJECTIVES: Despite successful antiretroviral (ARV) therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately-chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement. DESIGN: Cross-sectional analysis of 134 PLWH on suppressive ARV therapy, 79 lifestyle-comparable HIV-negative controls aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors (BD). METHODS: Biological age was estimated using a validated algorithm based on ten biomarkers. Associations between 'age advancement' (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression. RESULTS: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6, 14.9) years] and HIV-negative [5.5 (3.8, 7.2) years] COBRA participants compared to BD [-7.0 (-4.1, -9.9) years, both p's < 0.001)], but also in HIV-positive compared to HIV-negative participants (p < 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8 T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1, 6.8) years among those with nadir CD4 < 200 cells/μL and by 0.1 (0.06, 0.2) years for each additional month of exposure to saquinavir. CONCLUSIONS: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared to BD, to which persistent CMV, HBV co-infection and CD8 T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure

    Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function

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    BACKGROUND: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people-living-with-HIV. We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multi-modal neuroimaging from the Co-morBidity in Relation to AIDS (COBRA) cohort. METHODS: Cognitive function, brain tissue volumes and white matter microstructure were assessed in 134 HIV-positive patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion and volumetric data, taking advantage of the complementary information they provide. RESULTS: Compared to the highly comparable control group, cognitive function was impaired in four out of the six cognitive domains tested (median global T-scores: 50.8 vs. 54.2, p<0.001). Patients had lower grey but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the grey matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV-infection and systemic immune activation. CONCLUSIONS: Cognitive impairment, lower grey matter volume and white matter microstructural abnormalities were evident in HIV-positive individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-positive individuals

    Análise da implantação do sistema de gestão dos resíduos sólidos recicláveis na Vila das Peças, Guaraqueçaba, Paraná, Brasil

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    Objectives: Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement. Design: Cross-sectional analysis of 134 PLWH on suppressive antiretroviral therapy, 79 lifestyle-comparable HIV-negative controls aged 45 years or older from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors. Methods: Biological age was estimated using a validated algorithm based on 10 biomarkers. Associations between ` age advancement' (biological minus chronological age) and HIV status/ parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression. Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6-14.9) years] and HIV-negative [5.5 (3.8-7.2) years] COBRA participants compared with blood donors [-7.0 (-4.1 to -9.9) years, both P's< 0.001)], but also in HIV-positive compared with HIV-negative participants (P< 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8 thorn T-cell count were each associated with increased age advancement, independently of HIV-status/ group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1-6.8) years among those with nadir CD4 thorn T-cell count less than 200 cells/ ml and by 0.1 (0.06-0.2) years for each additional month of exposure to saquinavir. Conclusion: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared with blood donors, to which persistent CMV, HBV co-infection and CD8(+) T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure
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