Determinants of the risk of dying of HIV/AIDS in a rural South African community over the period of the decentralised roll-out of antiretroviral therapy: a longitudinal study.

Antiretroviral treatment (ART) has significantly reduced HIV mortality in South Africa. The benefits have not been experienced by all groups. Here we investigate the factors associated with these inequities. This study was located in a rural South African setting and used data collected from 2007 to 2010, the period when decentralised ART became available. Approximately one-third of the population were of Mozambican origin. There was a pattern of repeated circular migration between urban areas and this community. Survival analysis models were developed to identify demographic, socioeconomic, and spatial risk factors for HIV mortality. Among the study population of 105,149 individuals, there were 2,890 deaths. The HIV/TB mortality rate decreased by 27% between 2007-2008 and 2009-2010. For other causes of death, the reduction was 10%. Bivariate analysis found that the HIV/TB mortality risk was lower for: those living within 5 km of the Bhubezi Community Health Centre; women; young adults; in-migrants with a longer period of residence; permanent residents; and members of households owning motorised transport, holding higher socioeconomic positions, and with higher levels of education. Multivariate modelling showed, in addition, that those with South Africa as their country of origin had an increased risk of HIV/TB mortality compared to those with Mozambican origins. For males, those of South African origin, and recent in-migrants, the risk of death associated with HIV/TB was significantly greater than that due to other causes. In this community, a combination of factors was associated with an increased risk of dying of HIV/TB over the period of the roll-out of ART. There is evidence for the presence of barriers to successful treatment for particular sub-groups in the population, which must be addressed if the recent improvements in population-level mortality are to be maintained

Kondo effect in an integer-spin quantum dot

The Kondo effect is a key many-body phenomenon in condensed matter physics. It concerns the interaction between a localised spin and free electrons. Discovered in metals containing small amounts of magnetic impurities, it is now a fundamental mechanism in a wide class of correlated electron systems. Control over single, localised spins has become relevant also in fabricated structures due to the rapid developments in nano-electronics. Experiments have already demonstrated artificial realisations of isolated magnetic impurities at metallic surfaces, nanometer-scale magnets, controlled transitions between two-electron singlet and triplet states, and a tunable Kondo effect in semiconductor quantum dots. Here, we report an unexpected Kondo effect realised in a few-electron quantum dot containing singlet and triplet spin states whose energy difference can be tuned with a magnetic field. This effect occurs for an even number of electrons at the degeneracy between singlet and triplet states. The characteristic energy scale is found to be much larger than for the ordinary spin-1/2 case.Comment: 12 page

Five-year trend of competitiveness and knowledge-gaining attitude of university students; Evaluation based on an event of continuing health sciences education

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The role of magnetic anisotropy in the Kondo effect

In the Kondo effect, a localized magnetic moment is screened by forming a correlated electron system with the surrounding conduction electrons of a non-magnetic host. Spin S=1/2 Kondo systems have been investigated extensively in theory and experiments, but magnetic atoms often have a larger spin. Larger spins are subject to the influence of magnetocrystalline anisotropy, which describes the dependence of the magnetic moment's energy on the orientation of the spin relative to its surrounding atomic environment. Here we demonstrate the decisive role of magnetic anisotropy in the physics of Kondo screening. A scanning tunnelling microscope is used to simultaneously determine the magnitude of the spin, the magnetic anisotropy and the Kondo properties of individual magnetic atoms on a surface. We find that a Kondo resonance emerges for large-spin atoms only when the magnetic anisotropy creates degenerate ground-state levels that are connected by the spin flip of a screening electron. The magnetic anisotropy also determines how the Kondo resonance evolves in a magnetic field: the resonance peak splits at rates that are strongly direction dependent. These rates are well described by the energies of the underlying unscreened spin states.Comment: 14 pages, 4 figures, published in Nature Physic

Assessment of 'on-treatment platelet reactivity' and relationship with cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis

INTRODUCTION: The relationship between on-treatment platelet reactivity and cerebral micro-embolic signals (MES) is unknown, and has not been previously simultaneously assessed in asymptomatic and symptomatic carotid stenosis patients. METHODS: Consecutive eligible patients with ≥ 50% asymptomatic or recently symptomatic carotid stenosis (≤ 4 weeks following TIA/ischaemic stroke) were recruited to this pilot study. Symptomatic patients were followed up to the ‘late’ phase (≥ 3 months) following symptom onset or carotid intervention; longitudinal data were analysed from symptomatic patients with data available at both time-points. Platelet function/reactivity was assessed with the PFA-100® to measure collagen-ADP (C-ADP) and collagen-epinephrine (C-EPI) closure times in citrate-anticoagulated whole blood. Bilateral simultaneous 1-hour transcranial Doppler ultrasound (TCD) monitoring of the middle cerebral arteries was performed to classify patients as MES + ve or MES − ve. RESULTS: 31 patients with ≥ 50% asymptomatic and 46 with early symptomatic carotid stenosis or occlusion were included. 35 symptomatic patients were followed up to the late phase (23 following carotid intervention). Prevalence of ‘high on-treatment platelet reactivity’ (HTPR) on the C-EPI cartridge did not differ between asymptomatic and symptomatic patients overall, but was lower in ‘symptomatic post-intervention’ than asymptomatic patients on aspirin monotherapy (10% vs. 50%; p = 0.03). The prevalence of HTPR on the C-EPI cartridge decreased between the early and late phases in symptomatic patients (63% vs. 34%; p = 0.017), including those on aspirin monotherapy (p = 0.016). There were no significant differences in HTPR status between asymptomatic vs. early or late symptomatic MES + ve or MES − ve patients. DISCUSSION: Carotid interventional treatment, presumably in combination with resolution of the acute phase response, may decrease the prevalence of HTPR in patients with recently symptomatic carotid stenosis over time. Preliminary subgroup analysis suggests that successful intervention may reduce the prevalence of aspirin-HTPR in symptomatic patients to lower levels than asymptomatic medically-treated patients on aspirin monotherapy. Larger, longitudinal studies are warranted to reassess the impact of more intensive secondary preventive treatment on ex vivo platelet function at different levels of shear stress in carotid stenosis patients

REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets