Identifying Trustworthy Experts: How Do Policymakers Find and Assess Public Health Researchers Worth Consulting or Collaborating With?

This paper reports data from semi-structured interviews on how 26 Australian civil servants, ministers and ministerial advisors find and evaluate researchers with whom they wish to consult or collaborate. Policymakers valued researchers who had credibility across the three attributes seen as contributing to trustworthiness: competence (an exemplary academic reputation complemented by pragmatism, understanding of government processes, and effective collaboration and communication skills); integrity (independence, "authenticity", and faithful reporting of research); and benevolence (commitment to the policy reform agenda). The emphases given to these assessment criteria appeared to be shaped in part by policymakers' roles and the type and phase of policy development in which they were engaged. Policymakers are encouraged to reassess their methods for engaging researchers and to maximise information flow and support in these relationships. Researchers who wish to influence policy are advised to develop relationships across the policy community, but also to engage in other complementary strategies for promoting research-informed policy, including the strategic use of mass media.     

Lack or Inhibition of Dopaminergic Stimulation Induces a Development Increase of Striatal Tyrosine Hydroxylase-Positive Interneurons

We examined the role of endogenous dopamine (DA) in regulating the number of intrinsic tyrosine hydroxylase-positive (TH⁺) striatal neurons using mice at postnatal day (PND) 4 to 8, a period that corresponds to the developmental peak in the number of these neurons. We adopted the strategy of depleting endogenous DA by a 2-day treatment with α-methyl-p-tyrosine (αMpT, 150 mg/kg, i.p.). This treatment markedly increased the number of striatal TH⁺ neurons, assessed by stereological counting, and the increase was highly correlated to the extent of DA loss. Interestingly, TH⁺ neurons were found closer to the clusters of DA fibers after DA depletion, indicating that the concentration gradient of extracellular DA critically regulates the distribution of striatal TH⁺ neurons. A single i.p. injection of the D1 receptor antagonist, {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 (0.1 mg/kg), the D2/D3 receptor antagonist, raclopride (0.1 mg/kg), or the D4 receptor antagonist, L-745,870 (5 mg/kg) in mice at PND4 also increased the number of TH⁺ neurons after 4 days. Treatment with the D1-like receptor agonist {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393 (10 mg/kg) or with the D2-like receptor agonist, quinpirole (1 mg/kg) did not change the number of TH⁺ neurons. At least the effects of {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 were prevented by a combined treatment with {"type":"entrez-protein","attrs":{"text":"SKF38393","term_id":"1157151916","term_text":"SKF38393"}}SKF38393. Immunohistochemical analysis indicated that striatal TH⁺ neurons expressed D2 and D4 receptors, but not D1 receptors. Moreover, treatment with the α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) (3.2 mg/kg) also increased the number of TH⁺ neurons. The evidence that DHβE mimicked the action of {"type":"entrez-protein","attrs":{"text":"SCH23390","term_id":"1052733334","term_text":"SCH23390"}}SCH23390 in increasing the number of TH⁺ neurons supports the hypothesis that activation of D1 receptors controls the number of striatal TH⁺ neurons by enhancing the release of acetylcholine. These data demonstrate for the first time that endogenous DA negatively regulates the number of striatal TH⁺ neurons by direct and indirect mechanisms mediated by multiple DA receptor subtypes.     

SU-8 based microprobes with integrated planar electrodes for enhanced neural depth recording

A gold nanoparticle, localised plasmon array biosensor using light scattering has been employed in the detection of allergen-specific antibodies in whole blood and sera. The array sensor was functionalized with four different allergens, cat dander (Fel d1), dust mite (Der p1), peanut allergen (Ara h1) and dog dander (Can f1) and immuno-kinetic assay was performed to detect their respective anti-allergen IgG antibodies. Specific positive responses to antibodies at a concentration of 25 nM were observed for Fel d1, Der p1, and Ara h1 allergens, while the Can f1 channel served as a reference control. The sensitivity was further enhanced using a secondary anti-IgG detection antibodies to give a limit of detection of 2 nM. The results indicate the potential for nanoparticle scattering multiplexed arrays to screen unprepared blood samples at point-of-care for assays of complex samples such as the whole blood.     

Granulocyte colony stimulating factor expands hematopoietic stem cells within the central but not endosteal bone marrow region

Granulocyte colony stimulating factor (G-CSF) is clinically well established for the mobilization of hematopoietic stem cells (HSC). Extensive data on the underlying mechanism of G-CSF induced mobilization is available; however, little is known regarding the functional effect of G-CSF on HSC within the bone marrow (BM). In this study we analyzed the proportion and number of murine HSC in the endosteal and central bone marrow regions after 4 days of G-CSF administration. We demonstrate that the number of HSC, defined as CD150(+)CD48(-)LSK cells (LSKSLAM cells), increased within the central BM region in response to G-CSF, but not within the endosteal BM region. In addition the level of CD150 and CD48 expression also increased on cells isolated from both regions. We further showed that G-CSF mobilized proportionally fewer LSKSLAM compared to LSK cells, mobilized LSKSLAM had colony forming potential and the presence of these cells can be used as a measure for mobilization efficiency. Together we provide evidence that HSC in the BM respond differently to G-CSF and this is dependent on their location. These findings will be valuable in developing new agents which specifically mobilize HSC from the endosteal BM region, which we have previously demonstrated to have significantly greater hematopoietic potential compared to their phenotypically identical counterparts located in other regions of the BM.     

Neuroprotective effects of toll-like receptor 4 antagonism in spinal cord cultures and in a mouse model of motor neuron degeneration

Sustained inflammatory reactions are common pathological events associated with neuron loss in neurodegenerative diseases. Reported evidence suggests that Toll-like receptor 4 (TLR4) is a key player of neuroinflammation in several neurodegenerative diseases. However, the mechanisms by which TLR4 mediates neurotoxic signals remain poorly understood. We investigated the role of TLR4 in in vitro and in vivo settings of motor neuron degeneration. Using primary cultures from mouse spinal cords, we characterized both the proinflammatory and neurotoxic effects of TLR4 activation with lipopolysaccharide (activation of microglial cells, release of proinflammatory cytokines and motor neuron death) and the protective effects of a cyanobacteria-derived TLR4 antagonist (VB3323). With the use of TLR4-deficient cells, a critical role of the microglial component with functionally active TLR4 emerged in this setting. The in vivo experiments were carried out in a mouse model of spontaneous motor neuron degeneration, the wobbler mouse, where we preliminarily confirmed a protective effect of TLR4 antagonism. Compared with vehicle- and riluzole-treated mice, those chronically treated with VB3323 showed a decrease in microglial activation and morphological alterations of spinal cord neurons and a better performance in the paw abnormality and grip-strength tests. Taken together, our data add new understanding of the role of TLR4 in mediating neurotoxicity in the spinal cord and suggest that TLR4 antagonists could be considered in future studies as candidate protective agents for motor neurons in degenerative diseases.     

General and hybrid correlation nuclear magnetic resonance analysis of phosphorus in Phytophthora palmivora

As a specific tumor marker, prostate-specific antigen (PSA) is widely used for the early diagnosis of prostate cancer. Sensitive and specific methods are required to improve the diagnostic accuracy of PSA detection. In the current study, we compared the immuno-polymerase chain reaction (immuno-PCR) method with the solid-phase proximity ligation assay (SP-PLA) with respect to the detection of PSA. Using oligonucleotide-labeled antibody probes, we used both immuno-PCR and SP-PLA to detect trace levels of PSA. The nucleic acid sequences can be monitored using real-time PCR. SP-PLA, however, was found to be superior in terms of both the detection limit and the dynamic range. To detect even lower levels of PSA, we used the loop-mediated isothermal amplification (LAMP) method to measure the levels of reporter DNA molecules in SP-PLA. The sensitivity of the LAMP method is 0.001 pM, which is approximately 100-fold higher than the sensitivities of the other assays. The results suggest that an SP-PLA- and LAMP-based protocol with oligonucleotide-labeled antibody probes may have great application in detecting PSA or other proteins present at trace levels.     

Mice fed on a diet enriched with genetically engineered multivitamin corn show no sub‐acute toxic effects and no sub‐chronic toxicity

Multivitamin corn is a novel genetically engineered variety that simultaneously produces high levels of β‐carotene, ascorbate and folate, and therefore has the potential to address simultaneously multiple micronutrient deficiencies caused by the lack of vitamins A, B9 and C in developing country populations. As part of the development process for genetically engineered crops and following European Food Safety Authority (EFSA) recommendations, multivitamin corn must be tested in whole food/feed sub‐chronic animal feeding studies to ensure there are no adverse effects, and potential allergens must be identified. We carried out a 28‐day toxicity assessment in mice, which showed no short‐term sub‐acute evidence of diet‐related adverse health effects and no difference in clinical markers (food consumption, body weight, organ/tissue weight, haematological and biochemical blood parameters and histopathology) compared to mice fed on a control diet. A subsequent 90‐day sub‐chronic feeding study again showed no indications of toxicity compared to mice fed on control diets. Our data confirm that diets enriched with multivitamin corn have no adverse effects on mice, do not induce any clinical signs of toxicity and do not contain known allergens.     

The Well London program - a cluster randomized trial of community engagement for improving health behaviors and mental wellbeing: baseline survey results

Background

The Well London program used community engagement, complemented by changes to the physical and social neighborhood environment, to improve physical activity levels, healthy eating, and mental wellbeing in the most deprived communities in London. The effectiveness of Well London is being evaluated in a pair-matched cluster randomized trial (CRT). The baseline survey data are reported here.

Methods

The CRT involved 20 matched pairs of intervention and control communities (defined as UK census lower super output areas (LSOAs); ranked in the 11% most deprived LSOAs in London by the English Indices of Multiple Deprivation) across 20 London boroughs. The primary trial outcomes, sociodemographic information, and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline: a cross-sectional, interviewer-administered adult household survey; a self-completed, school-based adolescent questionnaire; a fieldworker completed neighborhood environmental audit. Baseline data collection occurred in 2008. Physical activity, healthy eating, and mental wellbeing were assessed using standardized, validated questionnaire tools. Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys.

Results

There were 4,107 adults and 1,214 adolescent respondents in the baseline surveys. The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics. The environmental characteristics of the intervention and control neighborhoods were broadly similar. There was greater between-cluster variation in the primary outcomes in the adult population compared to the adolescent population. Levels of healthy eating, smoking, and self-reported anxiety/depression were similar in the Well London adult population and the national Health Survey for England. Levels of physical activity were higher in the Well London adult population but this is likely to be due to the different measurement tools used in the two surveys.

Conclusions

Randomization of social interventions such as Well London is acceptable and feasible and in this study the intervention and control arms are well-balanced with respect to the primary outcomes and key sociodemographic characteristics. The matched design has improved the statistical efficiency of the study amongst adults but less so amongst adolescents. Follow-up data collection will be completed 2012.

Trial registration

Current Controlled Trials ISRCTN68175121