International study into the use of intermittent hormone therapy in the treatment of carcinoma of the prostate : A meta-analysis of 1446 patients

OBJECTIVE: To review pooled phase II data to identify features of different regimens of intermittent hormone therapy (IHT), developed to reduce the morbidity of treating metastatic prostate cancer, and which carries a theoretical advantage of delaying the onset of androgen-independent prostate cancer, (AIPC) that are associated with success, highlighting features which require exploration with prospective trials to establish the best strategies for using this treatment. METHODS: Individual data were collated on 1446 patients with adequate information, from 10 phase II studies with >50 cases, identified through Pubmed. RESULTS: Univariate and multivariate Cox proportional hazard models were developed to predict treatment success with a high degree of statistical success. The prostate-specific antigen (PSA) nadir, the PSA threshold to restart treatment, and medication type and duration, were important predictors of outcome. CONCLUSIONS: The duration of biochemical remission after a period of HT is a durable early indicator of how rapidly AIPC and death will occur, and will make a useful endpoint in future trials to investigate the best ways to use IHT based on the important treatment cycling variables described above. Patients spent a mean of 39% of the time off treatment. The initial PSA level and PSA nadir allow the identification of patients with prostate cancer in whom it might be possible to avoid radical therapy.Peer reviewe

Shifts in Plankton, Nutrient and Light Relationships in Small Tundra Lakes Caused by Localized Permafrost Thaw

Tundra lakes located in the Mackenzie Delta uplands, NWT, Canada, are increasingly being affected by permafrost thaw in the form of shoreline retrogressive thaw slumping. This form of thaw-induced disturbance is used as a surrogate indicator of landscape-related disturbance linked to regional climate warming. We compared 22 lakes, half affected by thaw slumping and half unaffected, to determine whether water column nutrient concentrations, light availability, and plankton biomass differed between these two lake types. Total phosphorus (TP), total dissolved nitrogen (TDN), dissolved organic carbon (DOC), and chlorophyll a concentrations were higher in unaffected lakes than in slump-affected lakes. Absorbance related to water colour of both UV and photosynthetically active radiation in the water column was also higher in unaffected lakes, but bacterioplankton abundance was not different between lake types. UV light absorbance was found to be the best predictor of pelagic chlorophyll a concentrations in unaffected lakes, whereas TDN (and to a lesser extent TP) were the best predictors of pelagic chlorophyll a in slump-affected lakes. These findings indicate that slumping arising from permafrost thaw produces a shift in tundra lake nutrient, light, and phytoplankton relationships. Given the projections of continued warming, this result has significant implications for the future biogeochemical and ecological states of Arctic tundra lakes.Les lacs de toundra situés dans les hautes terres du delta du Mackenzie, dans les Territoires du Nord-Ouest, au Canada, sont de plus en plus touchés par le dégel du pergélisol en ce sens qu’il y a glissement régressif du littoral dû au dégel. Cette forme de perturbation attribuable au dégel sert d’indicateur auxiliaire en matière de perturbation du paysage liée au réchauffement climatique de la région. Nous avons comparé 22 lacs, dont la moitié était touchée par le glissement dû au dégel et l’autre moitié ne l’était pas, afin de déterminer si les concentrations en nutriments des colonnes d’eau, la disponibilité lumineuse et la biomasse du plancton différaient entre ces deux types de lacs. Les concentrations de phosphore total (PT), d’azote dissous total (ADT), de carbone organique dissous (COD) et de chlorophylle a étaient plus élevées dans les lacs non touchés quand dans les lacs où il y avait glissement du littoral. L’absorbance liée à la couleur de l’eau du rayonnement actif photosynthétique et du rayonnement actif ultraviolet dans les colonnes d’eau était également plus élevée dans les lacs non touchés, mais l’abondance du bactérioplancton ne différait pas d’un type de lac à l’autre. On a déterminé que l’absorbance de lumière ultraviolette était le meilleur prédicteur de concentrations de chlorophylle a pélagique dans les lacs non touchés, tandis que l’ADT (et le PT, dans une moindre mesure) constituaient les meilleurs prédicteurs de chlorophylle a pélagique pour ce qui est des lacs faisant l’objet d’un glissement. Ces constatations indiquent que le glissement attribuable au dégel du pergélisol altère les relations qui existent entre les nutriments, la lumière et le phytoplancton des lacs de toundra. Compte tenu des projections à l’égard d’un réchauffement continuel, ce résultat revêt d’importantes incidences sur les états biogéochimiques et écologiques des lacs de la toundra arctique

Where did all the pangolins go? International CITES trade in pangolin species

Available online 24 October 2016The pangolin is greatly sought after for its various body parts, largely driven by demand from China. The mammal has been driven to the edge of extinction in Asia, with two Asian species listed as Critically Endangered in the International Union for Conservation of Nature Red List. With declining Asian pangolin populations, a shift in trade from Asian to African pangolin species has been suggested. The Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) Trade Database provides a unique opportunity to investigate global trends in pangolin trade at the species level, across a broad temporal scale (1977–2014). We found that CITES trade in Asian pangolin species decreased through time, whilst trade in African species increased post 2000. The total number of incidents involving Asian species declined since 2000, yet they were still being traded in large volumes (more than 17,500 estimated whole Asian pangolins were traded from 2001 to 2014) despite a zero export quota for all wild sourced Asian species, traded for primarily commercial purposes. In 2014 all eight pangolin species were recorded in the CITES trade for the first time. An increasingly complex international network was identified through time, with the United States of America (US) being the dominant player in the global pangolin trade that was reported to CITES. The US was the most frequent trade country throughout the entire period and was the greatest importer of pangolins, and their products; measured both in volume as well as frequency. We hope that identifying these global trade network characteristics, and pangolin trade dynamics will help to inform pangolin conservation efforts, and guide enforcement and legislative changes in the future.Sarah Heinrich, Talia A. Wittmann, Thomas A.A. Prowse, Joshua V. Ross, Steven Delean, Chris R. Shepherd, Phillip Casse

Dynamic simulation of the THAI heavy oil recovery process

Toe-to-Heel Air Injection (THAI) is a variant of conventional In-Situ Combustion (ISC) that uses a horizontal production well to recover mobilised partially upgraded heavy oil. It has a number of advantages over other heavy oil recovery techniques such as high recovery potential. However, existing models are unable to predict the effect of the most important operational parameters, such as fuel availability and produced oxygen concentration, which will give rise to unsafe designs. Therefore, we have developed a new model that accurately predicts dynamic conditions in the reservoir and also is easily scalable to investigate different field scenarios. The model used a three component direct conversion cracking kinetics scheme, which does not depend on the stoichiometry of the products and, thus, reduces the extent of uncertainty in the simulation results as the number of unknowns is reduced. The oil production rate and cumulative oil produced were well predicted, with the latter deviating from the experimental value by only 4%. The improved ability of the model to emulate real process dynamics meant it also accurately predicted when the oxygen was first produced, thereby enabling a more accurate assessment to be made of when it would be safe to shut-in the process, prior to oxygen breakthrough occurring. The increasing trend in produced oxygen concentration following a step change in the injected oxygen rate by 33 % was closely replicated by the model. The new simulations have now elucidated the mechanism of oxygen production during the later stages of the experiment. The model has allowed limits to be placed on the air injection rates that ensure stability of operation. Unlike previous models, the new simulations have provided better quantitative prediction of fuel laydown, which is a key phenomenon that determines whether, or not, successful operation of the THAI process can be achieved. The new model has also shown that, for completely stable operation, the combustion zone must be restricted to the upper portion of the sand pack, which can be achieved by using higher producer back pressure

The H-Dibaryon and the Hard Core

The H dibaryon, a single, triply magic bag containing two up, two down and two strange quarks, has long been sought after in a variety of experiments. Its creation has been attempted in $K^-$, proton and most recently in relativistic heavy ion induced reactions. We concentrate on the latter, but our conclusions are more generally applicable. The two baryons coalescing to form the single dibaryon, likely $\Lambda \Lambda$ in the case of heavy ions, must penetrate the short range repulsive barrier which is expected to exist between them. We find that this barrier can profoundly affect the probability of producing the H state, should it actually exist.Comment: 9 pages including 4 figure

The Lambda-Lambda Interaction and ^{6}_{Lambda Lambda}He

An OBE potential model for the ^{1}S_0 S = -2 interaction is analyzed with emphasis on the role of coupling between the Lambda Lambda, N Xi, and Sigma Sigma channels. Singlet scalar exchange, an approximation to two-pion exchange, is significant in all channels; surprisingly, the one-pion exchange component is almost negligible. The size of the channel coupling as a function of the overall strength of the OBE model potential is examined. Implications of the analysis for the binding energy of ^{6}_{Lambda Lambda}He are considered; the new experimental datum may suggest a consistency between the extracted Lambda Lambda matrix element and the relation implied by SU(3) among OBE baryon-baryon interactions. \\Comment: 4 pages brief report to Physical Review

Stochastic Variational Search for ΛΛ4^{4}_{\Lambda\Lambda}H

A four-body calculation of the $pn\Lambda\Lambda$ bound state, $^{\ 4}_{\Lambda\Lambda}$H, is performed using the stochastic variational method and phenomenological potentials. The$NN$,$\Lambda N$, and$\Lambda\Lambda$potentials are taken from a recent Letter by Filikhin and Gal, PRL{\bf 89}, 172502 (2002). Although their Faddeev-Yakubovsky calculation found no bound-state solution over a wide range of$\Lambda\Lambda$interaction strengths, the present variational calculation gives a bound-state energy, which is clearly lower than the$_\Lambda^3{H}+\Lambda$threshold, even for a weak$\Lambda\Lambda$interaction strength deduced from a recent experimental$B_{\Lambda\Lambda}(^{6}_{\Lambda\Lambda}{He})$value. The binding energies obtained are close to, and slightly larger than, the values obtained from the three-body$d\Lambda\Lambda$ model in the Letter.Comment: Corrected typos, added addtional calculations regarding a truncated to l=0 interaction model, 4 pages, 3 figure

Brueckner Rearrangement Effects in Λ5^5_\LambdaHe and ΛΛ6^6_{\Lambda\Lambda}He

Rearrangement effects in light hypernuclei are investigated in the framework of the Brueckner theory. We can estimate without detailed numerical calculations that the energy of the $\alpha$-core is reduced by more than 2.5 MeV when the $\Lambda$ adheres to $^4$He to form $^5_\Lambda$He. Similar assessment of rearrangement contributions is essential to deduce the strength of $\Lambda\Lambda$ interaction from experimentally observed $\Delta B_{\Lambda\Lambda}$. The recently observed experimental value of $\sim$ 1 MeV for the $\Delta B_{\Lambda\Lambda}$ of \hll suggests that the matrix element of $$ in \hll is around -2 MeV.Comment: 7 pages, to appear in Phys. Rev.

GLI1 confers profound phenotypic changes upon LNCaP prostate cancer cells that include the acquisition of a hormone independent state

The GLI (GLI1/GLI2) transcription factors have been implicated in the development and progression of prostate cancer although our understanding of how they actually contribute to the biology of these common tumours is limited. We observed that GLI reporter activity was higher in normal (PNT-2) and tumourigenic (DU145 and PC-3) androgen-independent cells compared to androgen-dependent LNCaP prostate cancer cells and, accordingly, GLI mRNA levels were also elevated. Ectopic expression of GLI1 or the constitutively active NGLI2 mutant induced a distinct cobblestone-like morphology in LNCaP cells that, regarding the former, correlated with increased GLI2 as well as expression of the basal/stem-like markers CD44, beta1-integrin, Np63 and BMI1, and decreased expression of the luminal marker AR (androgen receptor). LNCaP-GLI1 cells were viable in the presence of the AR inhibitor bicalutamide and gene expression profiling revealed that the transcriptome of LNCaP-GLI1 cells was significantly closer to DU145 and PC-3 cells than to control LNCaP-pBP (empty vector) cells, as well as identifying LCN2/NGAL as a highly induced transcript which is associated with hormone independence in breast and prostate cancer. Functionally, LNCaP-GLI1 cells displayed greater clonal growth and were more invasive than control cells but they did not form colonies in soft agar or prostaspheres in suspension suggesting that they do not possess inherent stem cell properties. Moreover, targeted suppression of GLI1 or GLI2 with siRNA did not reverse the transformed phenotype of LNCaP-GLI1 cells nor did double GLI1/GLI2 knockdowns activate AR expression in DU145 or PC-3 cells. As such, early targeting of the GLI oncoproteins may hinder progression to a hormone independent state but a more detailed understanding of the mechanisms that maintain this phenotype is required to determine if their inhibition will enhance the efficacy of anti-hormonal therapy through the induction of a luminal phenotype and increased dependency upon AR function