In-vivo studies of targeted and localized cancer drug release from microporous poly-di-methyl-siloxane (PDMS) devices for the treatment of triple negative breast cancer.

Triple-negative breast cancer (TNBC) treatment is challenging and frequently characterized by an aggressive phenotype and low prognosis in comparison to other subtypes. This paper presents fabricated implantable drug-loaded microporous poly-di-methyl-siloxane (PDMS) devices for the delivery of targeted therapeutic agents [Luteinizing Hormone-Releasing Hormone conjugated paclitaxel (PTX-LHRH) and Luteinizing Hormone-Releasing Hormone conjugated prodigiosin (PG-LHRH)] for the treatment and possible prevention of triple-negative cancer recurrence. In vitro assessment using the Alamar blue assay demonstrated a significant reduction (p < 0.05) in percentage of cell growth in a time-dependent manner in the groups treated with PG, PG-LHRH, PTX, and PTX-LHRH. Subcutaneous triple-negative xenograft breast tumors were then induced in athymic female nude mice that were four weeks old. Two weeks later, the tumors were surgically but partially removed, and the device implanted. Mice were observed for tumor regrowth and organ toxicity. The animal study revealed that there was no tumor regrowth, six weeks post-treatment, when the LHRH targeted drugs (LHRH-PTX and LHRH-PGS) were used for the treatment. The possible cytotoxic effects of the released drugs on the liver, kidney, and lung are assessed using quantitative biochemical assay from blood samples of the treatment groups. Ex vivo histopathological results from organ tissues showed that the targeted cancer drugs released from the implantable drug-loaded device did not induce any adverse effect on the liver, kidneys, or lungs, based on the results of qualitative toxicity studies. The implications of the results are discussed for the targeted and localized treatment of triple negative breast cancer.

Ecohydrological threats to Colophospermum mopane in southern Zimbabwe.

Rapid ecohydrological changes in semi-arid landscapes are increasingly threatening humanity's life-support systems and eroding many of the ecosystem services (ESs) upon which humans occupying such regions depend. Knowing which services and ecohydrological changes to be most concerned about is indispensable to maintaining the general health of such ecosystems and for developing effective ecosystem management practices. In the semi-arid regions of southwestern Zimbabwe where a large population of rural households depend on ESs extracted from the Colophospermum mopane tree, such understanding may be critical in reversing potential ES losses that may have catastrophic effects on the lives of many. We surveyed a total of 127 rural households who occupy the semi-arid landscapes of the Colophospermum mopane belt in southern Zimbabwe. We assessed the ecohydrological conditions characterising ecosystems where they obtain ES provisioning goods using a number of ecohydrological variables commonly cited in the literature on ecohydrology. Building on principal component analysis (PCA), we employed a hierarchical agglomerative clustering method to create unique clusters of households that depicted different levels of risks or threats associated with their ES provisioning harvesting practices. Multiple regression analysis was further performed to identify significant ecohydrological cluster-defining variables. Our results showed that spatial differences in ecohydrological parameters resulted in four distinct ES resource thresholds depicting four categories of risks that households face in extracting such resources in nearby landscapes. We concluded by proposing a number of landscape restoration or management practices targeted at reversing potential ES losses and subsequently safeguarding the livelihoods of many who depend on ESs.

A novel microcrystalline tyrosine-adsorbed, mite-allergoid subcutaneous immunotherapy: 1-year follow-up report.

AIM: A 1-year follow-up study comparing the safety and tolerability of the dosing schedules, satisfaction and effectiveness of a novel microcrystalline tyrosine-adsorbed mite (Dermatophagoides pteronyssinus)-allergoid subcutaneous immunotherapy (Acarovac Plus™) in 30 adult patients (18-65 years) with allergic rhinitis and/or asthma. MATERIALS & METHODS: The effectiveness of the product was assessed by nasal provocation test measuring peak nasal inspiratory flow/symptoms, in vitro immunologic changes (IgE, IgG4 and IL-10) and Treatment Satisfaction Questionnaire for Medication. RESULTS: No adverse events were reported during dosing schedules. Significant decreases in symptom scores and drop of peak nasal inspiratory flow in follow-up visits (4 weeks and 1 year) were recorded. Significant increases in IgG4-specific antibody titers and IL-10 were exhibited. CONCLUSION: Significant decreases in clinical symptoms and immunological parameters were observed, accompanying a high level of patient satisfaction and tolerance.

The climateprediction.net BBC climate change experiment: design of the coupled model ensemble.

Perturbed physics experiments are among the most comprehensive ways to address uncertainty in climate change forecasts. In these experiments, parameters and parametrizations in atmosphere-ocean general circulation models are perturbed across ranges of uncertainty, and results are compared with observations. In this paper, we describe the largest perturbed physics climate experiment conducted to date, the British Broadcasting Corporation (BBC) climate change experiment, in which the physics of the atmosphere and ocean are changed, and run in conjunction with a forcing ensemble designed to represent uncertainty in past and future forcings, under the A1B Special Report on Emissions Scenarios (SRES) climate change scenario.

Uncertainty in predictions of the climate response to rising levels of greenhouse gases.

The range of possibilities for future climate evolution needs to be taken into account when planning climate change mitigation and adaptation strategies. This requires ensembles of multi-decadal simulations to assess both chaotic climate variability and model response uncertainty. Statistical estimates of model response uncertainty, based on observations of recent climate change, admit climate sensitivities--defined as the equilibrium response of global mean temperature to doubling levels of atmospheric carbon dioxide--substantially greater than 5 K. But such strong responses are not used in ranges for future climate change because they have not been seen in general circulation models. Here we present results from the 'climateprediction.net' experiment, the first multi-thousand-member grand ensemble of simulations using a general circulation model and thereby explicitly resolving regional details. We find model versions as realistic as other state-of-the-art climate models but with climate sensitivities ranging from less than 2 K to more than 11 K. Models with such extreme sensitivities are critical for the study of the full range of possible responses of the climate system to rising greenhouse gas levels, and for assessing the risks associated with specific targets for stabilizing these levels.