Young caregivers in the context of the HIV/AIDS pandemic in sub-Saharan Africa

Against a background of rising adult mortality and morbidity in the context of the HIV/AIDS pandemic in sub-Saharan Africa, this paper provides both quantitative and qualitative evidence for the existence of a largely neglected group of young people with increased responsibility for caregiving. Using questionnaire surveys, focus groups, storyboards and in-depth interviews in three studies across Southern and Eastern Africa some young people in Lesotho, Tanzania and Zimbabwe are found to devote considerable time and energy to caring for sick members of their households. Examination of the tasks carried out by these youngsters finds them to be burdened beyond usual familial and societal expectations of children's 'normal' contributions to the reproduction of households via domestic chores and suchlike. It is concluded that these young people can be described as 'young carers'. The three studies are presented to illuminate different sociospatial aspects of caregiving by young people. First, using qualitative data from Lesotho the range of caring tasks young caregivers; perform for care recipients - usually a grandmother, parent, or sibling - is identified. Second, the impact caregiving responsibilities have on children's primary school attendance is examined using survey data from Tanzania. Third, the wider negative and positive impacts of caregiving including loss of friends and gaining of emotional maturity for young carers and their households is explored with in-depth individual interviews from Zimbabwe. Finally, suggestions are made for further research to deepen understanding of the geographies of caring within the context of the population geographies of the HIV/AIDS pandemic in sub-Saharan Africa and beyond. Copyright (c) 2006 John Wiley & Sons, Ltd.

An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro

G-protein-coupled receptors are desensitized by a two-step process. In a first step, G-protein-coupled receptor kinases (GRKs) phosphorylate agonist-activated receptors that subsequently bind to a second class of proteins, the arrestins. GRKs can be classified into three subfamilies, which have been implicated in various diseases. The physiological role(s) of GRKs have been difficult to study as selective inhibitors are not available. We have used SELEX (systematic evolution of ligands by exponential enrichment) to develop RNA aptamers that potently and selectively inhibit GRK2. This process has yielded an aptamer, C13, which bound to GRK2 with a high affinity and inhibited GRK2-catalyzed rhodopsin phosphorylation with an IC50 of 4.1 nM. Phosphorylation of rhodopsin catalyzed by GRK5 was also inhibited, albeit with 20-fold lower potency (IC50 of 79 nM). Furthermore, C13 reveals significant specificity, since almost no inhibitory activity was detectable testing it against a panel of 14 other kinases. The aptamer is two orders of magnitude more potent than the best GRK2 inhibitors described previously and shows high selectivity for the GRK family of protein kinases.

A square-planar nickel(II) monoradical complex with a bis(salicylidene)diamine ligand

The new square-planar Ni-II-N2O2 complex [Ni(L-Me)] (1(Me)), where L-Me, stands for the dianionic phenolato form of N,N'bis(3,5-di-tert-butyl-salicylidene)-4,5-dimethyl-1,2-phenyl- enediamine ((LH2)-L-Me), has been synthesised and fully characterised. X-ray crystallography was also used for the characterisation. The electrochemical one-electron oxidation of 1(Me) produces the thermally stable (within the temperature range 10-295 K) cationic species (1(Me))(+). The UV/Vis and X-band EPR experimental data, supported by DFT calculations, indicate that (1(Me))(+), is best described as a Ni-II monoradical complex and, thus, does NOT exist in a Ni-III ground state, in contrast to its demethylated counterpart [Ni(L-H)](+) (1(H))(+) below 170 K.

The D2 antagonist sulpiride modulates the neural processing of both rewarding and aversive stimuli in healthy volunteers.

Rationale: Animal studies indicate that dopamine pathways in the ventral striatum code for the motivational salience of both rewarding and aversive stimuli, but evidence for this mechanism in humans is less established. We have developed a functional magnetic resonance imaging (fMRI) model which permits examination of the neural processing of both rewarding and aversive stimuli. Objectives: The aim of the study was to determine the effect of the dopamine receptor antagonist, sulpiride, on the neural processing of rewarding and aversive stimuli in healthy volunteers. Methods: We studied 30 healthy participants who were randomly allocated to receive a single dose of sulpiride (400 mg) or placebo, in a double-blind, parallel-group design. We used fMRI to measure the neural response to rewarding (taste or sight of chocolate) and aversive stimuli (sight of mouldy strawberries or unpleasant strawberry taste) 4 h after drug treatment. Results: Relative to placebo, sulpiride reduced blood oxygenation level-dependent responses to chocolate stimuli in the striatum (ventral striatum) and anterior cingulate cortex. Sulpiride also reduced lateral orbitofrontal cortex and insula activations to the taste and sight of the aversive condition. Conclusions: These results suggest that acute dopamine receptor blockade modulates mesolimbic and mesocortical neural activations in response to both rewarding and aversive stimuli in healthy volunteers. This effect may be relevant to the effects of dopamine receptor antagonists in the treatment of psychosis and may also have implications for the possible antidepressant properties of sulpiride.

Climate models without pre-industrial volcanic forcing underestimate historical ocean thermal expansion

Episodic explosive volcanic eruptions are a natural part of the climate system but are often omitted from atmosphere-ocean general circulation model (AOGCM) preindustrial spin-up and control experiments. This omission imposes a negative bias on ocean heat uptake in simulations of the historical period. In models of a range of complexity, we find that global-mean sea level rise due to thermal expansion during the last ∼ 150 years is consequently underestimated by 5–30 mm, which is a substantial proportion of the model mean of 50 mm in Coupled Model Intercomparison Project Phase 3 AOGCMs with anthropogenic forcing only, and is therefore important in accounting for 20th century sea level rise. We test and recommend a procedure for removing the bias.

Climate impact research: beyond patchwork

Despite significant progress in climate impacts research, the narratives that science can presently piece together of a 2-, 3-, 4-, or 5-degree warmer world remain fragmentary. Here we briefly review past undertakings to comprehensively characterize and quantify climate impacts based on multi-model approaches. We then report on the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), a community-driven effort to systematically compare impacts models across sectors and scales, and to quantify the uncertainties along the chain from greenhouse gas emissions and climate input data to the modelling of climate impacts themselves. We show how ISI-MIP and similar efforts can substantially advance the science relevant to impacts, adaptation and vulnerability, and we outline the steps that need to be taken in order to make the most of available modelling tools. We discuss pertinent limitations of these methods and how they could be tackled. We argue that it is time to consolidate the current patchwork of impacts knowledge through integrated cross-sectoral assessments, and that the climate impacts community is now in a favourable position to do so.

A traceable physical calibration of the vertical advection-diffusion equation for modelling ocean heat uptake

The classic vertical advection-diffusion (VAD) balance is a central concept in studying the ocean heat budget, in particular in simple climate models (SCMs). Here we present a new framework to calibrate the parameters of the VAD equation to the vertical ocean heat balance of two fully-coupled climate models that is traceable to the models’ circulation as well as to vertical mixing and diffusion processes. Based on temperature diagnostics, we derive an effective vertical velocity w∗ and turbulent diffusivity k∗ for each individual physical process. In steady-state, we find that the residual vertical velocity and diffusivity change sign in mid-depth, highlighting the different regional contributions of isopycnal and diapycnal diffusion in balancing the models’ residual advection and vertical mixing. We quantify the impacts of the time-evolution of the effective quantities under a transient 1%CO2 simulation and make the link to the parameters of currently employed SCMs.