Peripherally acting mu-opioid antagonist for the treatment of opioid-induced constipation: Systematic review and meta-analysis

Background and Aim Opioid-induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting mu-opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated. Methods We conducted a quantitative meta-analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases. Results We included 31 RCTs with 7849 patients. A meta-analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18-1.68; n = 5622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55-2.12; n = 4821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, -0.22; 95% CI, -0.28 to -0.17; n = 2884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06-1.15; n = 7715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85-1.28; n = 5890). Conclusion Peripherally acting mu-opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta-analysis. The possibility of publication bias was the limitation of this study.ArticleJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY.34(5):818-829(2019)journal articl

20 questions on Adaptive Dynamics

Abstract Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss

Protocols for BNCT of glioblastoma multiforme at Brookhaven: Practical considerations

In this report we discuss some issues considered in selecting initial protocols for boron neutron capture therapy (BNCT) of human glioblastoma multiforme. First the tolerance of normal tissues, especially the brain, to the radiation field. Radiation doses limits were based on results with human and animal exposures. Estimates of tumor control doses were based on the results of single-fraction photon therapy and single fraction BNCT both in humans and experimental animals. Of the two boron compounds (BSH and BPA), BPA was chosen since a FDA-sanctioned protocol for distribution in humans was in effect at the time the first BNCT protocols were written and therapy studies in experimental animals had shown it to be more effective than BSH

Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood

We measured mobility patterns that describe walking trajectories of individual Me'Phaa peasants searching and collecting fuelwood in the forests of "La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow a mixed pattern of nearly-constant steps when individuals displace from their homes towards potential collecting sites and a mixed pattern of steps of different lengths when actually searching for fallen wood in the forest. Displacements in the searching phase seem not to be compatible with L\'evy flights described by power-laws with optimal scaling exponents. These findings however can be interpreted in the light of deterministic searching on heavily degraded landscapes where the interaction of the individuals with their scarce environment produces alternative searching strategies than the expected L\'evy flights. These results have important implications for future management and restoration of degraded forests and the improvement of the ecological services they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The final publication will be available at http://www.springerlink.co

Biomechanical modeling of the small intestine as required for the design and operation of a robotic endoscope

This paper discusses biomechanical issues that are related to the locomotion of a robotic endoscope in the human small intestine. The robot propels itself by pushing against the intestinal walls, much like a pipe crawler. However, the small intestine is not a rigid pipe; and locomotion in it is further complicated by the fact that the bowel is susceptible to damage. With the goal of engineering a safe and reliable machine, the biomechanical properties of the small bowel are studied and related to the mechanics of robotic endoscope locomotion through the small intestine

Dispersal and population structure at different spatial scales in the subterranean rodent Ctenomys australis

<p>Abstract</p> <p><b>Background</b></p> <p>The population genetic structure of subterranean rodent species is strongly affected by demographic (e.g. rates of dispersal and social structure) and stochastic factors (e.g. random genetic drift among subpopulations and habitat fragmentation). In particular, gene flow estimates at different spatial scales are essential to understand genetic differentiation among populations of a species living in a highly fragmented landscape. <it>Ctenomys australis </it>(the sand dune tuco-tuco) is a territorial subterranean rodent that inhabits a relatively secure, permanently sealed burrow system, occurring in sand dune habitats on the coastal landscape in the south-east of Buenos Aires province, Argentina. Currently, this habitat is threatened by urban development and forestry and, therefore, the survival of this endemic species is at risk. Here, we assess population genetic structure and patterns of dispersal among individuals of this species at different spatial scales using 8 polymorphic microsatellite loci. Furthermore, we evaluate the relative importance of sex and habitat configuration in modulating the dispersal patterns at these geographical scales.</p> <p>Results</p> <p>Our results show that dispersal in <it>C. australis </it>is not restricted at regional spatial scales (~ 4 km). Assignment tests revealed significant population substructure within the study area, providing support for the presence of two subpopulations from three original sampling sites. Finally, male-biased dispersal was found in the Western side of our study area, but in the Eastern side no apparent philopatric pattern was found, suggesting that in a more continuous habitat males might move longer distances than females.</p> <p>Conclusions</p> <p>Overall, the assignment-based approaches were able to detect population substructure at fine geographical scales. Additionally, the maintenance of a significant genetic structure at regional (~ 4 km) and small (less than 1 km) spatial scales despite apparently moderate to high levels of gene flow between local sampling sites could not be explained simply by the linear distance among them. On the whole, our results support the hypothesis that males disperse more frequently than females; however they do not provide support for strict philopatry within females.</p

The effects of linkage disequilibrium in large scale SNP datasets for MDR

<p>Abstract</p> <p>Background</p> <p>In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package.</p> <p>Results</p> <p>Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases.</p> <p>Conclusions</p> <p>Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset.</p