A systematic review of the effectiveness of docetaxel and mitoxantrone for the treatment of metastatic hormone-refractory prostate cancer

A systematic review was performed to evaluate the clinical effectiveness of docetaxel in combination with prednisolone (docetaxel is licensed in the UK for use in combination with prednisone or prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer. Prednisone is not used in the UK, but it is reasonable to use docetaxel plus prednisone data in this review of docetaxel plus prednisolone) for the treatment of metastatic hormone-refractory prostate cancer. A scoping search identified a trial of docetaxel plus prednisone vs mitoxantrone plus prednisone, but did not identify any trials comparing docetaxel plus prednisolone/prednisone with any other treatments. Therefore, we considered additional indirect evidence that would enable a comparison of docetaxel plus prednisolone/prednisone with other chemotherapy regimens and active supportive care. Systematic searching (upto April 2005) identified seven randomised controlled trials. One large well-conducted trial assessed docetaxel plus prednisone vs mitoxantrone plus prednisone; this showed statistically significant improvements with 3-weekly docetaxel in terms of overall survival, quality of life, pain response and PSA decline. Two other chemotherapy regimens that included docetaxel with estramustine also showed improved outcomes in comparison with mitoxantrone plus prednisone. Three trials that compared mitoxantrone plus corticosteroids with corticosteroids alone were identified and their results for overall survival combined, which showed very little difference between the two groups. The addition of clodronate to mitoxantrone plus prednisone showed no significant differences in comparison with mitoxantrone plus prednisone alone. The evidence suggests that chemotherapy regimens containing 3-weekly docetaxel are superior to mitoxantrone or corticosteroids alone

Survival After Lung Transplantation of Cystic Fibrosis Patients Infected with Burkholderia cepacia Complex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71603/1/j.1600-6143.2008.02186.x.pd

Evaluating Knowledge Anchors in Data Graphs against Basic Level Objects

The growing number of available data graphs in the form of RDF Linked Da-ta enables the development of semantic exploration applications in many domains. Often, the users are not domain experts and are therefore unaware of the complex knowledge structures represented in the data graphs they in-teract with. This hinders users’ experience and effectiveness. Our research concerns intelligent support to facilitate the exploration of data graphs by us-ers who are not domain experts. We propose a new navigation support ap-proach underpinned by the subsumption theory of meaningful learning, which postulates that new concepts are grasped by starting from familiar concepts which serve as knowledge anchors from where links to new knowledge are made. Our earlier work has developed several metrics and the corresponding algorithms for identifying knowledge anchors in data graphs. In this paper, we assess the performance of these algorithms by considering the user perspective and application context. The paper address the challenge of aligning basic level objects that represent familiar concepts in human cog-nitive structures with automatically derived knowledge anchors in data graphs. We present a systematic approach that adapts experimental methods from Cognitive Science to derive basic level objects underpinned by a data graph. This is used to evaluate knowledge anchors in data graphs in two ap-plication domains - semantic browsing (Music) and semantic search (Ca-reers). The evaluation validates the algorithms, which enables their adoption over different domains and application contexts

Even Between-Lap Pacing Despite High Within-Lap Variation During Mountain Biking

Purpose: Given the paucity of research on pacing strategies during competitive events, this study examined changes in dynamic high-resolution performance parameters to analyze pacing profiles during a multiple-lap mountain-bike race over variable terrain. Methods: A global-positioning-system (GPS) unit (Garmin, Edge 305, USA) recorded velocity (m/s), distance (m), elevation (m), and heart rate at 1 Hz from 6 mountain-bike riders (mean ± SD age = 27.2 ± 5.0 y, stature = 176.8 ± 8.1 cm, mass = 76.3 ± 11.7 kg, VO2max = 55.1 ± 6.0 mL · kg–1 . min–1) competing in a multilap race. Lap-by-lap (interlap) pacing was analyzed using a 1-way ANOVA for mean time and mean velocity. Velocity data were averaged every 100 m and plotted against race distance and elevation to observe the presence of intralap variation. Results: There was no significant difference in lap times (P = .99) or lap velocity (P = .65) across the 5 laps. Within each lap, a high degree of oscillation in velocity was observed, which broadly reflected changes in terrain, but high-resolution data demonstrated additional nonmonotonic variation not related to terrain. Conclusion: Participants adopted an even pace strategy across the 5 laps despite rapid adjustments in velocity during each lap. While topographical and technical variations of the course accounted for some of the variability in velocity, the additional rapid adjustments in velocity may be associated with dynamic regulation of self-paced exercise

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Inferring hidden Markov models from noisy time sequences: a method to alleviate degeneracy in molecular dynamics

We present a new method for inferring hidden Markov models from noisy time sequences without the necessity of assuming a model architecture, thus allowing for the detection of degenerate states. This is based on the statistical prediction techniques developed by Crutchfield et al., and generates so called causal state models, equivalent to hidden Markov models. This method is applicable to any continuous data which clusters around discrete values and exhibits multiple transitions between these values such as tethered particle motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The algorithms developed have been shown to perform well on simulated data, demonstrating the ability to recover the model used to generate the data under high noise, sparse data conditions and the ability to infer the existence of degenerate states. They have also been applied to new experimental FRET data of Holliday Junction dynamics, extracting the expected two state model and providing values for the transition rates in good agreement with previous results and with results obtained using existing maximum likelihood based methods.Comment: 19 pages, 9 figure

Constraints to Implementing the Essential Health Package in Malawi

Increasingly seen as a useful tool of health policy, Essential or Minimal Health Packages direct resources to interventions that aim to address the local burden of disease and be cost-effective. Less attention has been paid to the delivery mechanisms for such interventions. This study aimed to assess the degree to which the Essential Health Package (EHP) in Malawi was available to its population and what health system constraints impeded its full implementation. The first phase of this study comprised a survey of all facilities in three districts including interviews with all managers and clinical staff. In the second and third phase, results were discussed with District Health Management Teams and national level stakeholders, respectively, including representatives of the Ministry of Health, Central Medical Stores, donors and NGOs. The EHP in Malawi is focussing on the local burden of disease; however, key constraints to its successful implementation included a widespread shortage of staff due to vacancies but also caused by frequent trainings and meetings (only 48% of expected man days of clinical staff were available; training and meetings represented 57% of all absences in health centres). Despite the training, the percentage of health workers aware of vital diagnostic and therapeutic approaches to EHP conditions was weak. Another major constraint was shortages of vital drugs at all levels of facilities (e.g. Cotrimoxazole was sufficiently available to treat the average number of patients in only 27% of health centres). Although a few health workers noted some improvement in infrastructure and working conditions, they still considered them to be widely inadequate. In Malawi, as in similar resource poor countries, greater attention needs to be given to the health system constraints to delivering health care. Removal of these constraints should receive priority over the considerable focus on the development and implementation of essential packages of interventions

The textual characteristics of traditional and Open Access scientific journals are similar

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an increased amount of natural language processing (NLP) work on full text biomedical journal publications. Much of this work is done with Open Access journal articles. Such work assumes that Open Access articles are representative of biomedical publications in general and that methods developed for analysis of Open Access full text publications will generalize to the biomedical literature as a whole. If this assumption is wrong, the cost to the community will be large, including not just wasted resources, but also flawed science. This paper examines that assumption.</p> <p>Results</p> <p>We collected two sets of documents, one consisting only of Open Access publications and the other consisting only of traditional journal publications. We examined them for differences in surface linguistic structures that have obvious consequences for the ease or difficulty of natural language processing and for differences in semantic content as reflected in lexical items. Regarding surface linguistic structures, we examined the incidence of conjunctions, negation, passives, and pronominal anaphora, and found that the two collections did not differ. We also examined the distribution of sentence lengths and found that both collections were characterized by the same mode. Regarding lexical items, we found that the Kullback-Leibler divergence between the two collections was low, and was lower than the divergence between either collection and a reference corpus. Where small differences did exist, log likelihood analysis showed that they were primarily in the area of formatting and in specific named entities.</p> <p>Conclusion</p> <p>We did not find structural or semantic differences between the Open Access and traditional journal collections.</p

Caterpillars and fungal pathogens: two co-occurring parasites of an ant-plant mutualism

In mutualisms, each interacting species obtains resources from its partner that it would obtain less efficiently if alone, and so derives a net fitness benefit. In exchange for shelter (domatia) and food, mutualistic plant-ants protect their host myrmecophytes from herbivores, encroaching vines and fungal pathogens. Although selective filters enable myrmecophytes to host those ant species most favorable to their fitness, some insects can by-pass these filters, exploiting the rewards supplied whilst providing nothing in return. This is the case in French Guiana for Cecropia obtusa (Cecropiaceae) as Pseudocabima guianalis caterpillars (Lepidoptera, Pyralidae) can colonize saplings before the installation of their mutualistic Azteca ants. The caterpillars shelter in the domatia and feed on food bodies (FBs) whose production increases as a result. They delay colonization by ants by weaving a silk shield above the youngest trichilium, where the FBs are produced, blocking access to them. This probable temporal priority effect also allows female moths to lay new eggs on trees that already shelter caterpillars, and so to occupy the niche longer and exploit Cecropia resources before colonization by ants. However, once incipient ant colonies are able to develop, they prevent further colonization by the caterpillars. Although no higher herbivory rates were noted, these caterpillars are ineffective in protecting their host trees from a pathogenic fungus, Fusarium moniliforme (Deuteromycetes), that develops on the trichilium in the absence of mutualistic ants. Therefore, the Cecropia treelets can be parasitized by two often overlooked species: the caterpillars that shelter in the domatia and feed on FBs, delaying colonization by mutualistic ants, and the fungal pathogen that develops on old trichilia. The cost of greater FB production plus the presence of the pathogenic fungus likely affect tree growth

The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns

Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research