Network based statistics reveals trophic and neuroprotective effect of early high dose erythropoetin on brain connectivity in very preterm infants.

Periventricular white matter injury is common in very preterm infants and it is associated with long term neurodevelopmental impairments. While evidence supports the protective effects of erythropoetin (EPO) in preventing injury, we currently lack the complete understanding of how EPO affects the emergence and maturation of anatomical brain connectivity and function. In this case-control study, connectomic analysis based on diffusion MRI tractography was applied to evaluate the effect of early high-dose EPO in preterm infants. A whole brain, network-level analysis revealed a sub-network of anatomical brain connections in which connectivity strengths were significantly stronger in the EPO group. This distributed network comprised connections predominantly in the frontal and temporal lobe bilaterally, and the effect of EPO was focused on peripheral and feeder connections of the core structural connectivity network. EPO resulted in a globally increased clustering coefficient, higher global and average local efficiency, while higher strength and increased clustering was found for regions in the frontal lobe and cingulate gyrus. The connectivity network most affected by the EPO treatment showed a steeper increase graph theoretical measures with age compared to the placebo group. Our results demonstrate a weak but widespread effect of EPO on the structural connectivity network and a possible trophic effect of EPO reflected by increasing network segregation, predominantly in local connections.

The effect of compression and decompression speed on the mechanical strength of compacts.

The purpose of this work was to investigate the effect of punch speed on the compaction properties of pharmaceutical powders; in particular, to separate out differences between the effect of the compression and decompression events. Tablets were prepared using an integrated compaction research system. Various "sawtooth" punch profiles were followed to compare the effects of different punch speeds on the crushing strength of the resulting tablets. The loading and unloading speeds were varied independently of one another. In general, when the compression speed was equal to the decompression speed, the tablet crushing strength was observed to decrease as the punch velocity increased. When the compression speed was greater than or less than the decompression speed, the results varied, depending on the material undergoing compaction. Reduction of the unloading speed from 300 to 10 mm/sec for pregelatinized starch and microcrystalline cellulose produced a significant increase in crushing strength, whereas no significant increase in crushing strength was observed until the loading speed was reduced to 10 mm/sec. Reduction of the unloading speed had a similar effect on the direct compression (DC) ibuprofen, however, even greater improvement in the crushing strength was observed when the loading speed was reduced. No improvement in the DC acetaminophen tablets was observed when the unloading speed was reduced, however, a significant increase in crushing strength was produced when the rate of loading was reduced. This work showed that the strength of tablets can be improved and some tableting problems such as capping can be minimized or prevented by modifying the rates of loading/unloading.

The influence of varying precompaction and main compaction profile parameters on the mechanical strength of compacts.

The purpose of this work was to investigate how altering the method of force application could be beneficial to tablet production in order to increase tablet strength and eliminate or minimize the incidence of capping and lamination. An integrated compaction research system (i.e., compaction simulator) was used throughout this study. Compaction profiles containing a single compaction event and a double (pre- and main) compaction event were created. The ratio and magnitude of the pre- and main compaction pressures were varied and the time interval between the pre- and main compaction events was altered to determine the effects on the crushing strengths and capping tendency of the final compacts. In all cases, for a given pressure, the double compaction event produced stronger tablets than the single compaction event. When the ratio and magnitude of the pre- and main compaction pressures were varied, the results differed depending on the material undergoing compaction. Dicalcium phosphate/microcrystalline cellulose and pregelatinized starch tablets had no significant difference in crushing strength values regardless of whether the precompaction pressure was less than or greater than the main compaction pressure. However, both direct compression (DC) acetaminophen and DC ibuprofen were found to have increased crushing strengths and decreased capping/lamination when the precompaction pressure was less than the main compaction pressure. When the time interval between the pre- and main compaction events was varied from 30 to 500 msec, no significant difference in the crushing strength or capping/lamination tendency was observed. It was concluded that the effect of altering the ratio and magnitude of the pre- and main compaction pressures varied from one material to another, suggesting that the profiles should be tailored individually for the specific material undergoing compaction.