NGOs and government partnership for health systems strengthening: A qualitative study presenting viewpoints of government, NGOs and donors in Pakistan

<p>Abstract</p> <p>Background</p> <p>Health systems are expected to serve the population needs in an effective, efficient and equitable manner. Therefore, the importance of strengthening of public, private and community health systems has been emphasized time and again. In most of the developing countries, certain weaknesses and gaps in the government health systems have been hampering the achievement of improved health outcomes. Public sector in Pakistan has been deficient in the capacity to deliver equitable and quality health services and thus has been grossly underutilized.</p> <p>Methods</p> <p>A qualitative study comprising in-depth interviews was conducted capturing the perceptions of the government functionaries, NGO representatives and donor community about the role and position of NGOs in health systems strengthening in Pakistan's context. Analysis of the data was done manually to generate nodes, sub-nodes and themes.</p> <p>Results</p> <p>Since many years, international and local non-governmental organizations (NGOs) have endeavored to fill the gaps in health service delivery, research and advocacy. NGOs have relatively performed better and achieved the results because of the flexible planning and the ability to design population based projects on health education, health promotion, social marketing, community development and advocacy. This paper captures the need and the opportunity of public private partnership in Pakistan and presents a framework for a meaningful engagement of the government and the private and nonprofit NGOs.</p> <p>Conclusion</p> <p>Involving the NGOs for health system strengthening may eventually contribute to create a healthcare system reflecting an increased efficiency, more equity and good governance in the wake of the Millennium Development Goals. Nevertheless, few questions need to be answered and pre-requisites have to be fulfilled before moving on.</p

Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

Testing the white dwarf mass-radius relationship with eclipsing binaries

We present high-precision, model-independent, mass and radius measurements for 16 white dwarfs in detached eclipsing binaries and combine these with previously published data to test the theoretical white dwarf mass–radius relationship. We reach a mean precision of 2.4 per cent in mass and 2.7 per cent in radius, with our best measurements reaching a precision of 0.3 per cent in mass and 0.5 per cent in radius. We find excellent agreement between the measured and predicted radii across a wide range of masses and temperatures. We also find the radii of all white dwarfs with masses less than 0.48 M⊙ to be fully consistent with helium core models, but they are on average 9 per cent larger than those of carbon–oxygen core models. In contrast, white dwarfs with masses larger than 0.52 M⊙ all have radii consistent with carbon–oxygen core models. Moreover, we find that all but one of the white dwarfs in our sample have radii consistent with possessing thick surface hydrogen envelopes (10−5 ≥ MH/MWD ≥ 10−4), implying that the surface hydrogen layers of these white dwarfs are not obviously affected by common envelope evolution

A preliminary study of genetic factors that influence susceptibility to bovine tuberculosis in the British cattle herd

Associations between specific host genes and susceptibility to Mycobacterial infections such as tuberculosis have been reported in several species. Bovine tuberculosis (bTB) impacts greatly the UK cattle industry, yet genetic predispositions have yet to be identified. We therefore used a candidate gene approach to study 384 cattle of which 160 had reacted positively to an antigenic skin test (‘reactors’). Our approach was unusual in that it used microsatellite markers, embraced high breed diversity and focused particularly on detecting genes showing heterozygote advantage, a mode of action often overlooked in SNP-based studies. A panel of neutral markers was used to control for population substructure and using a general linear model-based approach we were also able to control for age. We found that substructure was surprisingly weak and identified two genomic regions that were strongly associated with reactor status, identified by markers INRA111 and BMS2753. In general the strength of association detected tended to vary depending on whether age was included in the model. At INRA111 a single genotype appears strongly protective with an overall odds ratio of 2.2, the effect being consistent across nine diverse breeds. Our results suggest that breeding strategies could be devised that would appreciably increase genetic resistance of cattle to bTB (strictly, reduce the frequency of incidence of reactors) with implications for the current debate concerning badger-culling

Validation and Use of 22Na Turnover to Measure Food Intake in Free-Ranging Lizards

As the food intake of free-ranging animals has proved to be difficult to measure by traditional means, the feasibility of using radioactive Na to measure food consumption in a small scincid lizard (Lampropholis guichenoti) was assessed. This technique has previously been used only for several species of mammal. A significant relationship between food intake and Na turnover was found in the laboratory, with Na turnover underestimating intake by 7.6%. The food intake of free-ranging members of a field population was estimated by 22Na turnover to be 9.55, 0.65, 9.39 and 13.75 mg dry weight (day)-1 during autumn, winter, spring and summer respectively. Estimates of assimilated and expended energy from these food intake values agree closely with data reported for other lizards using alternative techniques. This study also describes the technical innovations which were necessary to study lizards weighing less than 1 g; and it suggests that 22Na can provide an easy, reliable and inexpensive means of studying the energetics of many free-living animals

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

Experimentally manipulated self-affirmation promotes reduced alcohol consumption in response to narrative information

Background: Health-risk information is increasingly being conveyed through accounts of personal experiences or narrative information. However, whether self-affirmation can enhance the ability of such messages to promote behavior change has yet to be established. Purpose: This study aims to test whether self-affirmation (a) promotes behavior change following exposure to narrative information about the risks of excessive alcohol consumption and (b) boosts message acceptance by increasing narrative engagement. Methods: In an experimental design, female drinkers (N = 142) reported their baseline alcohol consumption and were randomly allocated to condition (Self-Affirmation, Control). All participants next watched an extract of a genuine narrative piece in which the central character discussed her liver disease and its link with her previous alcohol consumption. Then, participants completed measures assessing engagement with the narrative and message acceptance. The primary outcome was alcohol consumption, assessed at 7-day follow-up. Results: Self-affirmed participants reported consuming significantly less alcohol at follow-up compared to baseline (mean 7-day decrease = 5.43 units); there was no change in alcohol consumption for the control group. Immediately post-manipulation, self-affirmed participants (vs. control) showed more message acceptance and reported greater engagement with the information. The impact of self-affirmation on message acceptance was mediated by narrative engagement. Conclusions: Self-affirmation can promote behavior change following exposure to health information, even when presented in narrative form

Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons

We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration

Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior

Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics