Joining the conspiracy? Negotiating ethics and emotions in researching (around) AIDS in southern Africa

AIDS is an emotive subject, particularly in southern Africa. Among those who have been directly affected by the disease, or who perceive themselves to be personally at risk, talking about AIDS inevitably arouses strong emotions - amongst them fear, distress, loss and anger. Conventionally, human geography research has avoided engagement with such emotions. Although the ideal of the detached observer has been roundly critiqued, the emphasis in methodological literature on 'doing no harm' has led even qualitative researchers to avoid difficult emotional encounters. Nonetheless, research is inevitably shaped by emotions, not least those of the researchers themselves. In this paper, we examine the role of emotions in the research process through our experiences of researching the lives of 'Young AIDS migrants' in Malawi and Lesotho. We explore how the context of the research gave rise to the production of particular emotions, and how, in response, we shaped the research, presenting a research agenda focused more on migration than AIDS. This example reveals a tension between universalised ethics expressed through ethical research guidelines that demand informed consent, and ethics of care, sensitive to emotional context. It also demonstrates how dualistic distinctions between reason and emotion, justice and care, global and local are unhelpful in interpreting the ethics of research practice

Nucleotide Discrimination with DNA Immobilized in the MspA Nanopore

Nanopore sequencing has the potential to become a fast and low-cost DNA sequencing platform. An ionic current passing through a small pore would directly map the sequence of single stranded DNA (ssDNA) driven through the constriction. The pore protein, MspA, derived from Mycobacterium smegmatis, has a short and narrow channel constriction ideally suited for nanopore sequencing. To study MspA's ability to resolve nucleotides, we held ssDNA within the pore using a biotin-NeutrAvidin complex. We show that homopolymers of adenine, cytosine, thymine, and guanine in MspA exhibit much larger current differences than in α-hemolysin. Additionally, methylated cytosine is distinguishable from unmethylated cytosine. We establish that single nucleotide substitutions within homopolymer ssDNA can be detected when held in MspA's constriction. Using genomic single nucleotide polymorphisms, we demonstrate that single nucleotides within random DNA can be identified. Our results indicate that MspA has high signal-to-noise ratio and the single nucleotide sensitivity desired for nanopore sequencing devices

The interpretation of systematic reviews with meta-analyses: an objective or subjective process?

<p>Abstract</p> <p>Background</p> <p>Discrepancies between the conclusions of different meta-analyses (quantitative syntheses of systematic reviews) are often ascribed to methodological differences. The objective of this study was to determine the discordance in interpretations when meta-analysts are presented with identical data.</p> <p>Methods</p> <p>We searched the literature for all randomized clinical trials (RCT) and review articles on the efficacy of intravenous magnesium in the early post-myocardial infarction period. We organized the articles chronologically and grouped them in packages. The first package included the first RCT, and a summary of the review articles published prior to first RCT. The second package contained the second and third RCT, a meta-analysis based on the data, and a summary of all review articles published prior to the third RCT. Similar packages were created for the 5^thRCT, 10^thRCT, 20^thRCT and 23^rdRCT (all articles). We presented the packages one at a time to eight different reviewers and asked them to answer three clinical questions after each package based solely on the information provided. The clinical questions included whether 1) they believed magnesium is now proven beneficial, 2) they believed magnesium will eventually be proven to be beneficial, and 3) they would recommend its use at this time.</p> <p>Results</p> <p>There was considerable disagreement among the reviewers for each package, and for each question. The discrepancies increased when the heterogeneity of the data increased. In addition, some reviewers became more sceptical of the effectiveness of magnesium over time, and some reviewers became less sceptical.</p> <p>Conclusion</p> <p>The interpretation of the results of systematic reviews with meta-analyses includes a subjective component that can lead to discordant conclusions that are independent of the methodology used to obtain or analyse the data.</p

Biomarker-indicated extent of oxidation of plant-derived organic carbon (OC) in relation to geomorphology in an arsenic contaminated Holocene aquifer, Cambodia

The poisoning of rural populations in South and Southeast Asia due to high groundwater arsenic concentrations is one of the world’s largest ongoing natural disasters. It is important to consider environmental processes related to the release of geogenic arsenic, including geomorphological and organic geochemical processes. Arsenic is released from sediments when iron-oxide minerals, onto which arsenic is adsorbed or incorporated, react with organic carbon (OC) and the OC is oxidised. In this study we build a new geomorphological framework for Kandal Province, a highly studied arsenic affected region of Cambodia, and tie this into wider regional environmental change throughout the Holocene. Analyses shows that the concentration of OC in the sediments is strongly inversely correlated to grainsize. Furthermore, the type of OC is also related to grain size with the clay containing mostly (immature) plant derived OC and sand containing mostly thermally mature derived OC. Finally, analyses indicate that within the plant derived OC relative oxidation is strongly grouped by stratigraphy with the older bound OC more oxidised than younger OC

The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans

The nematode, Caenorhabditis elegans, possesses the most extensive known superfamily of cys-loop ligand-gated ion channels (cys-loop LGICs) consisting of 102 subunit-encoding genes. Less than half of these genes have been functionally characterised which include cation-permeable channels gated by acetylcholine (ACh) and γ-aminobutyric acid (GABA) as well as anion-selective channels gated by ACh, GABA, glutamate and serotonin. Following the guidelines set for genetic nomenclature for C. elegans, we have designated unnamed subunits as lgc genes (ligand-gated ion channels of the cys-loop superfamily). Phylogenetic analysis shows that several of these lgc subunits form distinct groups which may represent novel cys-loop LGIC subtypes

A Project Portfolio Management Approach to Tacklingthe Exploration/Exploitation Trade-off

Organizational ambidexterity (OA) is an essen-tial capability for surviving in dynamic business environ-ments that advocates the simultaneous engagement inexploration and exploitation. Over the last decades,knowledge on OA has substantially matured, coveringinsights into antecedents, outcomes, and moderators of OA.However, there is little prescriptive knowledge that offersguidance on how to put OA into practice and to tackle thetrade-off between exploration and exploitation. To addressthis gap, the authors adopt the design science researchparadigm and propose an economic decision model asartifact. The decision model assists organizations inselecting and scheduling exploration and exploitation pro-jects to become ambidextrous in an economically reason-able manner. As for justificatory knowledge, the decisionmodel draws from prescriptive knowledge on projectportfolio management and value-based management, andfrom descriptive knowledge related to OA to structure thefield of action. To evaluate the decision model, its designspecification is discussed against theory-backed designobjectives and with industry experts. The paper alsoinstantiates the decision model as a software prototype andapplies the prototype to a case based on real-world data

Cholesterol treatment with statins: Who is left out and who makes it to goal?

<p>Abstract</p> <p>Background</p> <p>Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education) are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C) therapy goals are not known. We examined socio-demographic factors associated with a) eligibility for statin therapy among those not on statins, and b) achievement of statin therapy goals.</p> <p>Methods</p> <p>Adults (21-79 years) participating in the United States (US) National Health and Nutrition Examination Surveys, 1999-2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III) on Treatment of High Cholesterol guidelines.</p> <p>Results</p> <p>Among 6,043 participants not taking statins, 10.4% were eligible. Adjusted predictors of statin eligibility among statin non-users were being older, male, poorer, and less educated. Hispanics were less likely to be eligible but not using statins, an effect that became non-significant with adjustment for language usually spoken at home. Among 537 persons taking statins, 81% were at LDL-C goal. Adjusted predictors of goal failure among statin users were being male and poorer. These risks were not attenuated by adjustment for healthcare access or utilization.</p> <p>Conclusion</p> <p>Among person's not taking statins, the socio-economically disadvantaged are more likely to be eligible and among those on statins, the socio-economically disadvantaged are less likely to achieve statin treatment goals. Further study is needed to identify specific amenable patient and/or physician factors that contribute to these disparities.</p

Nitrated α-Synuclein Induces the Loss of Dopaminergic Neurons in the Substantia Nigra of Rats

BACKGROUND: The pathology of Parkinson's disease (PD) is characterized by the degeneration of the nigrostriatal dopaminergic pathway, as well as the formation of intraneuronal inclusions known as Lewy bodies and Lewy neurites in the substantia nigra. Accumulations of nitrated alpha-synuclein are demonstrated in the signature inclusions of Parkinson's disease. However, whether the nitration of alpha-synuclein is relevant to the pathogenesis of PD is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, effect of nitrated alpha-synuclein to dopaminergic (DA) neurons was determined by delivering nitrated recombinant TAT-alpha-synuclein intracellular. We provide evidence to show that the nitrated alpha-synuclein was toxic to cultured dopaminergic SHSY-5Y neurons and primary mesencephalic DA neurons to a much greater degree than unnitrated alpha-synuclein. Moreover, we show that administration of nitrated alpha-synuclein to the substantia nigra pars compacta of rats caused severe reductions in the number of DA neurons therein, and led to the down-regulation of D(2)R in the striatum in vivo. Furthermore, when administered to the substantia nigra of rats, nitrated alpha-synuclein caused PD-like motor dysfunctions, such as reduced locomotion and motor asymmetry, however unmodified alpha-synuclein had significantly less severe behavioral effects. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that alpha-synuclein, principally in its nitrated form, induce DA neuron death and may be a major factor in the etiology of PD