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Summary Time‐lapse seismology is important for monitoring subsurface pressure changes and fluid movements in producing hydrocarbon reservoirs. We analyse two 4‐D, 3C onshore surveys from Vacuum Field, New Mexico, USA, where the reservoir of interest is a fractured dolomite. In Phase VI, a time‐lapse survey was acquired before and after a pilot tertiary‐recovery programme of overpressured CO2 injection, which altered the fluid composition and the pore‐fluid pressure. Phase VII was a similar time‐lapse survey in the same location but with a different lower‐pressure injection regime. Applying a processing sequence to the Phase VI data preserving normal‐incidence shear‐wave anisotropy (time‐delays and polarization) and maximizing repeatability, interval‐time analysis of the reservoir interval shows a significant 10 per cent change in shear‐wave velocity anisotropy and 3 per cent decrease in the P‐wave interval velocities. A 1‐D model incorporating both saturation and pressure changes is matched to the data. The saturation changes have little effect on the seismic velocities. There are two main causes of the time‐lapse changes. Any change in pore‐fluid pressures modifies crack aspect ratios. Additionally, when there are overpressures, as there are in Phase VI, there is a 90° change in maximum impedance directions, and the leading faster split shear wave, instead of being parallel to the crack face as it is for low pore‐fluid pressures, becomes orthogonal to the crack face. The anisotropic poro‐elasticity (APE) model of the evolution of microcracked rock, calculates the evolution of cracked rock to changing conditions. APE modelling shows that at high overburden pressures only nearly vertical cracks, to which normal incidence P waves are less sensitive than S waves, remain open as the pore‐fluid pressure increases. APE modelling matches the observed time‐lapse effects almost exactly demonstrating that shear‐wave anisotropy is a highly sensitive diagnostic of pore‐fluid pressure changes in fractured reservoirs. In this comparatively limited analysis, APE modelling of fluid‐injection at known pressure correctly predicted the changes in seismic response, particularly the shear‐wave splitting, induced by the high‐pressure CO2 injection. In the Phase VII survey, APE modelling also successfully predicted the response to the lower‐pressure injection using the same Phase VI model of the cracked reservoir. The underlying reason for this remarkable predictability of fluid‐saturated reservoir rocks is the critical nature and high crack density of the fluid‐saturated cracks and microcracks in the reservoir rock, which makes cracked reservoirs critical systems.

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD.

Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly and activating the proapoptotic signal pathway. Vinorelbine and docetaxel have been approved for treating several advanced cancers. However, their efficacy in the management of advanced hormone-refractory prostate cancer remains to be clarified. Microtubule damage by some anticancer drugs can activate the ERK survival pathway, which conversely compromises chemotherapeutic efficacy. We analyzed the effect of ERK inhibitors PD98059 and U0126 on vinorelbine-and docetaxelinduced cell growth suppression of androgen-independent prostate cancer cells. In androgen-independent C-81 LNCaP cells, inhibition of ERK by PD98059, but not U0126, plus docetaxel resulted in enhanced growth suppression by an additional 20% compared to the sum of each agent alone (p < 0.02). The combination treatment of docetaxel plus PD98059 also increased cellular apoptosis, which was in part due to the inactivation of Bcl-2 by increasing phosphorylated Bcl-2 by more than 6-fold and Bax expression by 3-fold over each agent alone. At these dosages, docetaxel alone caused only marginal phosphorylation of Bcl-2 (10%). Docetaxel plus U0126 had only 20% added effect on Bcl-2 phosphorylation compared to docetaxel alone. Nevertheless, both U0126 and PD98059 exhibited an enhanced effect on docetaxel-induced growth suppression in PC-3 cells. No enhanced effect was observed for vinorelbine plus PD98059 or U0126. Thus, the combination therapy of docetaxel plus PD98059 may represent a new anticancer strategy, requiring lower drug dosages compared to docetaxel monotherapy. This may lower the cytotoxicity and enhance tumor suppression in vivo. This finding of a combination effect could be of potential clinical importance in treating hormone-refractory prostate cancer. © 2003 Wiley-Liss, Inc. Key words: prostate cancer; ERK inhibitor; apoptosis; chemotherapyProstate carcinoma is the most common malignancy and second leading cause of cancer death in men in the United States. 1 Approximately 180,400 new cases of prostate cancer are diagnosed each year. 2 Prostate cancers generally respond to androgen ablation therapy. However, such treatment is not curative, and the disease progresses to an androgen-independent stage. 3 Effective treatment for advanced hormone-refractory cancers remains a significant challenge. Conventional chemotherapy is usually ineffective because of the low proliferation rate of prostate cancer cells and the significant drug toxicity. 4 Thus, novel approaches are needed to serve this patient population.A wide range of anticancer drugs induce apoptosis in malignant cells. 5-7 DNA fragmentation, nuclear condensation and cell shrinkage are the typical markers of apoptosis. 8 The Bcl-2 family of proteins represents a critical checkpoint within most apoptotic pathways. 9 At least 15 family members have been identified in mammalian cells. These proteins form heterodimers of anti-and proapoptotic members to inhibit one another's function. 9 The ratio of ...

Background Research-based exercise interventions improve health-related quality of life (HRQL) and mobility in people with Parkinson’s disease (PD). Objective To examine whether exercise habits were associated with changes in HRQL and mobility over two years. Methods We identified a cohort of National Parkinson Foundation Quality Improvement Initiative (NPF-QII) participants with three visits. HRQL and mobility were measured with the Parkinson’s Disease Questionnaire (PDQ-39) and Timed Up and Go (TUG). We compared self-reported regular exercisers (≥2.5 hours/week) with people who did not exercise 2.5 hours/week. Then we quantified changes in HRQL and mobility associated with 30-minute increases in exercise, across PD severity, using mixed effects regression models. Results Participants with three observational study visits (n = 3408) were younger, with milder PD, than participants with fewer visits. After 2 years, consistent exercisers and people who started to exercise regularly after their baseline visit had smaller declines in HRQL and mobility than non-exercisers (p < 0.05). Non-exercisers worsened by 1.37 points on the PDQ-39 and a 0.47 seconds on the TUG per year. Increasing exercise by 30 minutes/week was associated with slower declines in HRQL (−0.16 points) and mobility (−0.04 sec). The benefit of exercise on HRQL was greater in advanced PD (−0.41 points) than mild PD (−0.14 points; p < 0.02). Conclusions Consistently exercising and starting regular exercise after baseline were associated with small but significant positive effects on HRQL and mobility changes over two years. The greater association of exercise with HRQL in advanced PD supports improving encouragement and facilitation of exercise in advanced PD.