Democracy – the real ‘ghost’ in the machine of global health policy Comment on “A ghost in the machine? politics in global health policy”

Politics is not the ghost in the machine of global health policy. Conceptually, it makes little sense to argue otherwise, while history is replete with examples of individuals and movements engaging politically in global health policy. Were one looking for ghosts, a more likely candidate would be democracy, which is currently under attack by a new global health technocracy. Civil society movements offer an opportunity to breathe life into a vital, but dying, political component of global health policy

Evaluation of low density array technology for quantitative parallel measurement of multiple genes in human tissue

BACKGROUND: Low density arrays (LDAs) have recently been introduced as a novel approach to gene expression profiling. Based on real time quantitative RT-PCR (QRT-PCR), these arrays enable a more focused and sensitive approach to the study of gene expression than gene chips, while offering higher throughput than more established approaches to QRT-PCR. We have now evaluated LDAs as a means of determining the expression of multiple genes simultaneously in human tissues and cells. RESULTS: Comparisons between LDAs reveal low variability, with correlation coefficients close to 1. By performing 2-fold and 10-fold serial dilutions of cDNA samples in the LDAs we determined a clear linear relationship between the gene expression data points over 5 orders of magnitude. We also showed that it is possible to use LDAs to accurately and quantitatively detect 2-fold changes in target copy number as well as measuring genes that are expressed with low and high copy numbers in the range of 1 × 10(2 )– 1 × 10(6 )copies. Furthermore, the data generated by the LDA from a cell based pharmacological study were comparable to data generated by conventional QRT-PCR. CONCLUSION: LDAs represent a valuable new approach for sensitive and quantitative gene expression profiling

Minimal Brownian Ratchet: An Exactly Solvable Model

We develop an exactly-solvable three-state discrete-time minimal Brownian ratchet (MBR), where the transition probabilities between states are asymmetric. By solving the master equations we obtain the steady-state probabilities. Generally the steady-state solution does not display detailed balance, giving rise to an induced directional motion in the MBR. For a reduced two-dimensional parameter space we find the null-curve on which the net current vanishes and detailed balance holds. A system on this curve is said to be balanced. On the null-curve, an additional source of external random noise is introduced to show that a directional motion can be induced under the zero overall driving force. We also indicate the off-balance behavior with biased random noise.Comment: 4 pages, 4 figures, RevTex source, General solution added. To be appeared in Phys. Rev. Let

Automatic blush detection in ‘concealed information’ test using visual stimuli

Blushing has been identified as an indicator of deception, shame, anxiety and embarrassment. Although normally associated with the skin coloration of the face, a blush response also affects skin surface temperature. In this paper, an approach to detect a blush response automatically is presented using the Argus P7225 thermal camera from e2v. The algorithm was tested on a sample population of 51 subjects, while using visual stimuli to elicit a response, and achieved recognition rates of ~77% TPR and ~60% TNR, indicating a thermal image sensor is the prospective device to pick up subtle temperature change synchronised with stimuli

'It's risky to walk in the city with syringes': understanding access to HIV/AIDS services for injecting drug users in the former Soviet Union countries of Ukraine and Kyrgyzstan

BACKGROUND: Despite massive scale up of funds from global health initiatives including the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) and other donors, the ambitious target agreed by G8 leaders in 2005 in Gleneagles to achieve universal access to HIV/AIDS treatment by 2010 has not been reached. Significant barriers to access remain in former Soviet Union (FSU) countries, a region now recognised as a priority area by policymakers. There have been few empirical studies of access to HIV/AIDS services in FSU countries, resulting in limited understanding and implementation of accessible HIV/AIDS interventions. This paper explores the multiple access barriers to HIV/AIDS services experienced by a key risk group-injecting drug users (IDUs). METHODS: Semi-structured interviews were conducted in two FSU countries-Ukraine and Kyrgyzstan-with clients receiving Global Fund-supported services (Ukraine n = 118, Kyrgyzstan n = 84), service providers (Ukraine n = 138, Kyrgyzstan n = 58) and a purposive sample of national and subnational stakeholders (Ukraine n = 135, Kyrgyzstan n = 86). Systematic thematic analysis of these qualitative data was conducted by country teams, and a comparative synthesis of findings undertaken by the authors. RESULTS: Stigmatisation of HIV/AIDS and drug use was an important barrier to IDUs accessing HIV/AIDS services in both countries. Other connected barriers included:criminalisation of drug use; discriminatory practices among government service providers; limited knowledge of HIV/AIDS, services and entitlements; shortages of commodities and human resources; and organisational, economic and geographical barriers. CONCLUSIONS: Approaches to thinking about universal access frequently assume increased availability of services means increased accessibility of services. Our study demonstrates that while there is greater availability of HIV/AIDS services in Ukraine and Kyrgyzstan, this does not equate with greater accessibility because of multiple, complex, and interrelated barriers to HIV/AIDS service utilisation at the service delivery level. Factors external to, as well as within, the health sector are key to understanding the access deficit in the FSU where low or concentrated HIV/AIDS epidemics are prevalent. Funders of HIV/AIDS programmes need to consider how best to tackle key structural and systemic drivers of access including prohibitionist legislation on drugs use, limited transparency and low staff salaries within the health sector

Unraveling the B. pseudomallei Heptokinase WcbL: from structure to drug discovery

Journal ArticleOpen Access funded by Biotechnology and Biological Sciences Research Council under a Creative Commons Attribution 4.0 International Public LicenseGram-negative bacteria utilize heptoses as part of their repertoire of extracellular polysaccharide virulence determinants. Disruption of heptose biosynthesis offers an attractive target for novel antimicrobials. A critical step in the synthesis of heptoses is their 1-O phosphorylation, mediated by kinases such as HldE or WcbL. Here, we present the structure of WcbL from Burkholderia pseudomallei. We report that WcbL operates through a sequential ordered Bi-Bi mechanism, loading the heptose first and then ATP. We show that dimeric WcbL binds ATP anti-cooperatively in the absence of heptose, and cooperatively in its presence. Modeling of WcbL suggests that heptose binding causes an elegant switch in the hydrogen-bonding network, facilitating the binding of a second ATP molecule. Finally, we screened a library of drug-like fragments, identifying hits that potently inhibit WcbL. Our results provide a novel mechanism for control of substrate binding and emphasize WcbL as an attractive anti-microbial target for Gram-negative bacteria.Biotechnology and Biological Sciences Research Counci

Optical Scattering from Vitreous Floaters

Vitreous “floaters” are a common entoptic phenomenon that can result in significant reduction in quality of life in a proportion of sufferers. The authors use a computational mathematical model based on Fourier optics and reflection and transmission coefficients calculated for a planar type II collagen opacity suspended in aqueous to show that floaters are perceived by the patient through interference effects that result in significant variations in intensity on the retina when viewing a constant brightness surface. The model also predicts that backscattered intensity from floaters is ten thousand to one million times lower than the variations in intensity produced on the retina, which demonstrates that the visible effects of floaters for the patient can be highly significant, whereas clinical observation of the vitreous may be entirely unremarkable. Importantly, the results also demonstrate that floaters do not need to be opaque to cause symptoms, with only small differences in refractive index between the floater material and the surrounding vitreous needed to produce significant optical effects. The model predicts that pupil size is an important factor in determining the severity of symptoms from floaters, with constricted pupils giving much greater effect than dilated pupils. Finally, the authors’ model predicts that floaters degrade contrast sensitivity function, with greatest degradation occurring in the 5–40 cycles per degree spatial frequency range and that the effects of shadowing caused by floaters are very strongly correlated to the predicted degradation of contrast sensitivity function.© 2021 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society

Phosphatidylinositol-4,5-bisphosphate is required for KCNQ1/KCNE1 channel function but not anterograde trafficking

The slow delayed-rectifier potassium current (IKs) is crucial for human cardiac action potential repolarization. The formation of IKs requires co-assembly of the KCNQ1 α-subunit and KCNE1 β-subunit, and mutations in either of these subunits can lead to hereditary long QT syndrome types 1 and 5, respectively. It is widely recognised that the KCNQ1/KCNE1 (Q1/E1) channel requires phosphatidylinositol-4,5-bisphosphate (PIP2) binding for function. We previously identified a cluster of basic residues in the proximal C-terminus of KCNQ1 that form a PIP2/phosphoinositide binding site. Upon charge neutralisation of these residues we found that the channel became more retained in the endoplasmic reticulum, which raised the possibility that channel-phosphoinositide interactions could play a role in channel trafficking. To explore this further we used a chemically induced dimerization (CID) system to selectively deplete PIP2 and/or phosphatidylinositol-4-phosphate (PI(4)P) at the plasma membrane (PM) or Golgi, and we subsequently monitored the effects on both channel trafficking and function. The depletion of PIP2 and/or PI(4)P at either the PM or Golgi did not alter channel cell-surface expression levels. However, channel function was extremely sensitive to the depletion of PIP2 at the PM, which is in contrast to the response of other cardiac potassium channels tested (Kir2.1 and Kv11.1). Surprisingly, when using the CID system IKs was dramatically reduced even before dimerization was induced, highlighting limitations regarding the utility of this system when studying processes highly sensitive to PIP2 depletion. In conclusion, we identify that the Q1/E1 channel does not require PIP2 or PI(4)P for anterograde trafficking, but is heavily reliant on PIP2 for channel function once at the PM.: This work was funded by the British Heart Foundation (BHF). BHF grant numbers: [FS/12/21/ 29482 and RG/15/15/31742]. S.C.H is supported by a BHF Intermediate Basic Science Research Fellowship [FS/12/59/29756]. The work was facilitated by The National Institute for Health Research Barts Biomedical Research Centre