Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat

<p>Abstract</p> <p>Background</p> <p>Hypoxia-ischemia (H-I) can produce widespread neurodegeneration and deep cerebral white matter injury in the neonate. Resident microglia and invading leukocytes promote lesion progression by releasing reactive oxygen species, proteases and other pro-inflammatory mediators. After injury, expression of the gelatin-degrading matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are thought to result in the proteolysis of extracellular matrix (ECM), activation of cytokines/chemokines, and the loss of vascular integrity. Thus, therapies targeting ECM degradation and progressive neuroinflammation may be beneficial in reducing H-I – induced neuropathy. Minocycline has MMP-inhibitory properties and is both anti-inflammatory and neuroprotective. AG3340 (prinomastat) is an MMP inhibitor with high selectivity for the gelatinases. The purpose of this study was to determine whether these compounds could limit H-I – induced injury when administered at a delayed time point.</p> <p>Methods</p> <p>Sprague-Dawley rats were exposed to H-I at postnatal day 7 (P7), consisting of unilateral carotid artery ligation followed by 90 min exposure to 8% O₂. Minocycline, AG3340, or vehicle were administered once daily for 6 days, beginning 24 hours after insult. Animals were sacrificed at P14 for neurohistological assessments. Immunohistochemistry was performed to determine the degree of reactive astrogliosis and immune cell activation/recruitment. Neural injury was detected using the Fluoro-Jade stain, a marker that identifies degenerating cells.</p> <p>Results</p> <p>CD11b and glial fibrillary acidic protein (GFAP) immunopositive cells increased in ipsilateral cortex after treatment with vehicle alone, demonstrating microglia/macrophage recruitment and reactive astrogliosis, respectively. Fluoro-Jade staining was markedly increased throughout the fronto-parietal cortex, striatum and hippocampus. Treatment with minocycline or AG3340 inhibited microglia/macrophage recruitment, attenuated astrogliosis and reduced Fluoro-Jade staining when compared to vehicle alone.</p> <p>Conclusion</p> <p>The selective gelatinase inhibitor AG3340 showed equal efficacy in reducing neural injury and dampening neuroinflammation when compared to the anti-inflammatory compound minocycline. Thus, MMP-2 and MMP-9 may be viable therapeutic targets to treat neonatal brain injury.</p

Public Sector Reform and Governance for Adaptation: Implications of New Public Management for Adaptive Capacity in Mexico and Norway

Although many governments are assuming the responsibility of initiating adaptation policy in relation to climate change, the compatibility of “governance-for-adaptation” with the current paradigms of public administration has generally been overlooked. Over the last several decades, countries around the globe have embraced variants of the philosophy of administration broadly called “New Public Management” (NPM) in an effort to improve administrative efficiencies and the provision of public services. Using evidence from a case study of reforms in the building sector in Norway, and a case study of water and flood risk management in central Mexico, we analyze the implications of the adoption of the tenets of NPM for adaptive capacity. Our cases illustrate that some of the key attributes associated with governance for adaptation—namely, technical and financial capacities; institutional memory, learning and knowledge; and participation and accountability—have been eroded by NPM reforms. Despite improvements in specific operational tasks of the public sector in each case, we show that the success of NPM reforms presumes the existence of core elements of governance that have often been found lacking, including solid institutional frameworks and accountability. Our analysis illustrates the importance of considering both longer-term adaptive capacities and short-term efficiency goals in public sector administration reform

HWVP submerged bed scrubber waste treatment by ion exchange at high pH

The Hanford Waste Vitrification Plant (HWVP) is expected to produce aqueous waste streams that will require further processing for cesium, strontium, and transuranic (TRU) removal prior to incorporation into grout. Fluor Daniel, Inc. has recommended that zeolite be added to these waste streams for adsorption of cesium (Cs) and strontium (Sr) following pH adjustment by sodium hydroxide (NAOH) addition. Filtration will then used to remove the TRU elements associated with the process solids and the zeolite containing the Cs and Sr

Internal deformation of the subducted Nazca slab inferred from seismic anisotropy

Within oceanic lithosphere a fossilized fabric is often preserved originating from the time of plate formation. Such fabric is thought to form at the mid-ocean ridge when olivine crystals align with the direction of plate spreading1, 2. It is unclear, however, whether this fossil fabric is preserved within slabs during subduction or overprinted by subduction-induced deformation. The alignment of olivine crystals, such as within fossil fabrics, can generate anisotropy that is sensed by passing seismic waves. Seismic anisotropy is therefore a useful tool for investigating the dynamics of subduction zones, but it has so far proved difficult to observe the anisotropic properties of the subducted slab itself. Here we analyse seismic anisotropy in the subducted Nazca slab beneath Peru and find that the fast direction of seismic wave propagation aligns with the contours of the slab. We use numerical modelling to simulate the olivine fabric created at the mid-ocean ridge, but find it is inconsistent with our observations of seismic anisotropy in the subducted Nazca slab. Instead we find that an orientation of the olivine crystal fast axes aligned parallel to the strike of the slab provides the best fit, consistent with along-strike extension induced by flattening of the slab during subduction (A. Kumar et al., manuscript in preparation). We conclude that the fossil fabric has been overprinted during subduction and that the Nazca slab must therefore be sufficiently weak to undergo internal deformation

Results from the dissemination of an evidence-based telephone-delivered intervention for healthy lifestyle and weight loss: the Optimal Health Program

Despite proven efficacy, there are few published evaluations of telephone-delivered interventions targeting physical activity, healthy eating, and weight loss in community dissemination contexts. This study aims to evaluate participant and program outcomes from the Optimal Health Program, a telephone-delivered healthy lifestyle and weight loss program provided by a primary health care organization. Dissemination study used a single-group, repeated measures design; outcomes were assessed at 6-month (mid-program; n = 166) and 12-month (end of program; n = 88) using paired analyses. The program reached a representative sample of at-risk, primary care patients, with 56 % withdrawing before program completion. Among completers, a statistically significant improvement between baseline and end of program was observed for weight [mean change (SE) −5.4 (7.0) kg] and waist circumference [−4.8 (9.7) cm], underpinned by significant physical activity and dietary change. Findings suggest that telephone-delivered weight loss and healthy lifestyle programs can provide an effective model for use in primary care settings, but participant retention remains a challenge

Non-Keynesian Effects of Fiscal Consolidations in Central Europe in the Years 2000-2013

Last two decades were a period of significant discussion concerning determinants of effectiveness of fiscal policy. After some cases of expansionary episodes of fiscal consolidations in eighties of XX century, an intensive international research on the possibility of non-Keynesian effects of fiscal contractions in highly developed countries has started. The aim of the article is to analyze the possibility of obtaining non-Keynesian effects of fiscal consolidations in post-transformation countries of Central Europe. An important aim of macroeconomic policy in the analyzed economies is to benefit the advantages of convergence process. Thus, the empirical analysis is made within conditional β-convergence framework. The verification of hypothesis of β-convergence enables to identify the long term tendency of output per capita, in the same time it enables to identify non-Keynesian effects of fiscal prudence and to assess their role in the process of reducing GDP gap between the analyzed economies. Then the potential transmission channels for non-Keynesian effects of fiscal policy were analyzed. In the research the data from Eurostat and European Commission for the years 2000-2013 was used. The paper provides arguments in favor of the existence of non-Keynesian effects of fiscal consolidations in Central Europe that support the process of conditional convergence

High-resolution Sr/Ca ratios in a Porites lutea coral from Lakshadweep Archipelago, southeast Arabian Sea: An example from a region experiencing steady rise in the reef temperature

Here we present the first record of Sr/Ca variability in a massive Porites lutea coral from the Lakshadweep Archipelago, Arabian Sea. The annual mean sea surface temperature (SST) in this region and the surrounding areas has increased steadily in the recent past. During some major El Nino events, SSTs are even higher, imposing additional thermal-stress on corals, episodically leading to coral bleaching. We infer from the coral-Sr/Ca record (1981-2008) that during some of these events high and persistent SSTs lead to a dampening of the temperature signal in coral-Sr/Ca, impairing the coral's ability to record full scale warming. Thus, coral-Sr/Ca may provide a history of past El Nino Southern-Oscillation (ENSO) induced thermal-stress episodes, which are a recurrent feature also seen in cross-spectral analysis between coral-Sr/Ca and the Nino3.4 index. Despite the impact of episodical thermal-stress during major El Nino events, our coral proxy faithfully records the seasonal monsoon-induced summer cooling on the order of approximate to 2.3 degrees C. Calibration of coral-Sr/Ca with instrumental grid-SST data shows significant correlation to regional SST and monsoon variability. Hence, massive Porites corals of this region are highly valuable archives for reconstructing long-term changes in SST, strongly influenced by monsoon variability on seasonal scales. More importantly, our data show that this site with increasing SST is an ideal location for testing the future effects of the projected anthropogenic SST increase on coral reefs that are already under thermal-stress worldwide

Climate change adaptation to escape the poverty trap: role of the private sector

Climate change adaptation and poverty alleviation call for an integrated strategy, because poverty exacerbates the vulnerability to climate change and vice versa. The private sector, which has traditionally been excluded from adaptation planning, may contribute greatly to the development of an integrated strategy. Here, we identify the differences in adaptation trajectories between the private sector and communities by proposing a conceptual framework and report on a case study in a dryland area of China, where the private sector led a successful adaptation and poverty alleviation project. We found that their win–win strategy achieved both climate change adaptation and development, thereby helping a disadvantaged community to escape the poverty trap and achieve sustainable development. The private sector played a dominant role in the response, as this sector can adapt in ways that are not possible for governments or communities. We suggest that participatory governance that includes private-sector stakeholders is more likely to achieve sustainable development

Characteristics of control group participants who increased their physical activity in a cluster-randomized lifestyle intervention trial

<p>Abstract</p> <p>Background</p> <p>Meaningful improvement in physical activity among control group participants in lifestyle intervention trials is not an uncommon finding, and may be partly explained by participant characteristics. This study investigated which baseline demographic, health and behavioural characteristics were predictive of successful improvement in physical activity in usual care group participants recruited into a telephone-delivered physical activity and diet intervention trial, and descriptively compared these characteristics with those that were predictive of improvement among intervention group participants.</p> <p>Methods</p> <p>Data come from the Logan Healthy Living Program, a primary care-based, cluster-randomized controlled trial of a physical activity and diet intervention. Multivariable logistic regression models examined variables predictive of an improvement of at least 60 minutes per week of moderate-to-vigorous intensity physical activity among usual care (n = 166) and intervention group (n = 175) participants.</p> <p>Results</p> <p>Baseline variables predictive of a meaningful change in physical activity were different for the usual care and intervention groups. Being retired and completing secondary school (but no further education) were predictive of physical activity improvement for usual care group participants, whereas only baseline level of physical activity was predictive of improvement for intervention group participants. Higher body mass index and being unmarried may also be predictors of physical activity improvement for usual care participants.</p> <p>Conclusion</p> <p>This is the first study to examine differences in predictors of physical activity improvement between intervention group and control group participants enrolled in a physical activity intervention trial. While further empirical research is necessary to confirm findings, results suggest that participants with certain socio-demographic characteristics may respond favourably to minimal intensity interventions akin to the treatment delivered to participants in a usual care group. In future physical activity intervention trials, it may be possible to screen participants for baseline characteristics in order to target minimal-intensity interventions to those most likely to benefit. (Australian Clinical Trials Registry, <url>http://www.anzctr.org.au/default.aspx</url>, ACTRN012607000195459)</p