Strategy and Action Plan for Sustainable Land Management in the High Pamir and Pamir-Alai Mountains

This Strategy and Action Plan was written within the framework of the project on Sustainable Land Management in the High Pamir and Pamir-Alai Mountains (PALM). PALM is an integrated transboundary initiative of the governments of the Kyrgyz Republic and the Republic of Tajikistan. It aims to address the interlinked problems of land degradation and poverty within a region that is one of Central Asia’s crucial sources of freshwater and a location of biodiversity hotspots. The project is executed by the Committee on Environment Protection in Tajikistan and the National Center for Mountain Regions Development in Kyrgyzstan, with fi nancial support from the Global Environment Facility (GEF) and other donors. The United Nations Environment Programme (UNEP) is the GEF Implementing Agency for the project, and the United Nations University (UNU) is the International Executing Agency. This Strategy and Action Plan integrates the work of three main teams of experts, namely the Pamir-Alai Transboundary Strategy and Action Plan (PATSAP) team, the Legal Task Forces, and a team of Natural Disaster Risk specialists. The PATSAP team was coordinated by the Centre for Development and Environment (CDE), University of Bern, Switzerland. The Legal Task Force was led by the Australian Centre for Agriculture and Law of the University of New England (UNE), and responsibility for the Natural Disaster Risk assessment was with the Central- Asian Institute of Applied Geosciences (CAIAG) in Bishkek, Kyrgyzstan. The development of the strategy took place from June 2009 to October 2010. The activities included fi eld study tours for updating the information base with fi rst-hand information from the local level, coordination meetings with actors from the region, and two multi-level stakeholder forums conducted in Khorog and Osh to identify priorities and to collect ideas for concrete action plans. The baseline information collected for the Strategy and Action Plan has been compiled by the experts and made available as reports1. A joint multi-level stakeholder forum was conducted in Jirgitol, Tajikistan, for in-depth discussion of the transboundary aspects. In August 2010, the draft Strategy and Action Plan was distributed among local, national, and international actors for consultation, and their comments were discussed at feedback forums in Khorog and Bishkek. This Strategy and Action Plan is intended as a recommendation. Nevertheless, it proposes concrete mechanisms for implementing the proposed sustainable land management (SLM) activities: The Regional Natural Resources Governance Framework provides the legal and policy concepts, principles, and regulatory requirements needed to create an enabling environment for SLM in the High Pamir and Pamir-Alai region at the transboundary, national, and local levels. The priority directions outlined provide a framework for the elaboration of rayon-level strategies and for strategies on specifi c topics (forestry, livestock, etc.), as well as for further development of government programmes and international projects. The action plans may serve as a pool of concrete ideas, which can be taken up by diff erent institutions and in smaller or larger projects. Finally, this document provides a basis for the elaboration and signing of targeted cooperation agreements on land use and management between the leaders of Osh oblast (Kyrgyz Republic), Gorno Badakhshan Autonomous Oblast, and Jirgitol rayon (Republic of Tajikistan).

Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

OBJECTIVES Previous studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis. METHODS Prospective cohort study of severe leptospirosis patients. Plasma levels of sE-selectin and Von Willebrand factor (VWF) were determined. Consequently, an in vitro endothelial cell model was used to assess endothelial activation after exposure to virulent Leptospira. Finally, immune activation, as a potential contributing factor to endothelial cell activation, was determined by soluble IL2-receptor (sIL-2r) and soluble Fas-ligand (sFasL) levels. RESULTS Plasma levels of sE-selectin and VWF strongly increased in patients compared to healthy controls. Furthermore, sE-selectin was significantly elevated (203 ng/ml vs. 157 ng/ml, p < 0.05) in survivors compared to non-survivors. Endothelial cells exposed to virulent Leptospira showed increased VWF expression. E-selectin and ICAM-1 expression did not change. Immunohistochemistry revealed the presence of intracellular Leptospira and qPCR suggested replication. In vivo analysis showed that increased levels of sFasL and sIL-2r were both strongly associated with mortality. Furthermore sIL-2r levels were increased in patients that developed bleeding and significantly correlated to duration of hospital stay. DISCUSSION Markers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients.

Increased levels of choline metabolites are an early marker of docetaxel treatment response in BRCA1-mutated mouse mammary tumors: an assessment by ex vivo proton magnetic resonance spectroscopy.

BACKGROUND Docetaxel is one of the most frequently used drugs to treat breast cancer. However, resistance or incomplete response to docetaxel is a major challenge. The aim of this study was to utilize MR metabolomics to identify potential biomarkers of docetaxel resistance in a mouse model for BRCA1-mutated breast cancer. METHODOLOGY High resolution magic angle spinning (HRMAS) (1)H MR spectroscopy was performed on tissue samples obtained from docetaxel-sensitive or -resistant BRCA1-mutated mammary tumors in mice. Measurements were performed on samples obtained before treatment and at 1-2, 3-5 and 6-7 days after a 25 mg/kg dose of docetaxel. The MR spectra were analyzed by multivariate analysis, followed by analysis of the signals of individual compounds by peak fitting and integration with normalization to the integral of the creatine signal and of all signals between 2.9 and 3.6 ppm. RESULTS The HRMAS spectra revealed significant metabolic differences between sensitive and resistant tissue samples. In particular choline metabolites were higher in resistant tumors by more than 50% with respect to creatine and by more than 30% with respect to all signals between 2.9 and 3.6 ppm. Shortly after treatment (1-2 days) the normalized choline metabolite levels were significantly increased by more than 30% in the sensitive group coinciding with the time of highest apoptotic activity induced by docetaxel. Thereafter, choline metabolites in these tumors returned towards pre-treatment levels. No change in choline compounds was observed in the resistant tumors over the whole time of investigation. CONCLUSIONS Relative tissue concentrations of choline compounds are higher in docetaxel resistant than in sensitive BRCA1-mutated mouse mammary tumors, but in the first days after docetaxel treatment only in the sensitive tumors an increase of these compounds is observed. Thus both pre- and post-treatment tissue levels of choline compounds have potential to predict response to docetaxel treatment.

Improving 4D plan quality for PBS-based liver tumour treatments by combining online image guided beam gating with rescanning.

Pencil beam scanned (PBS) proton therapy has many advantages over conventional radiotherapy, but its effectiveness for treating mobile tumours remains questionable. Gating dose delivery to the breathing pattern is a well-developed method in conventional radiotherapy for mitigating tumour-motion, but its clinical efficiency for PBS proton therapy is not yet well documented. In this study, the dosimetric benefits and the treatment efficiency of beam gating for PBS proton therapy has been comprehensively evaluated. A series of dedicated 4D dose calculations (4DDC) have been performed on 9 different 4DCT(MRI) liver data sets, which give realistic 4DCT extracting motion information from 4DMRI. The value of 4DCT(MRI) is its capability of providing not only patient geometries and deformable breathing characteristics, but also includes variations in the breathing patterns between breathing cycles. In order to monitor target motion and derive a gating signal, we simulate time-resolved beams' eye view (BEV) x-ray images as an online motion surrogate. 4DDCs have been performed using three amplitude-based gating window sizes (10/5/3 mm) with motion surrogates derived from either pre-implanted fiducial markers or the diaphragm. In addition, gating has also been simulated in combination with up to 19 times rescanning using either volumetric or layered approaches. The quality of the resulting 4DDC plans has been quantified in terms of the plan homogeneity index (HI), total treatment time and duty cycle. Results show that neither beam gating nor rescanning alone can fully retrieve the plan homogeneity of the static reference plan. Especially for variable breathing patterns, reductions of the effective duty cycle to as low as 10% have been observed with the smallest gating rescanning window (3 mm), implying that gating on its own for such cases would result in much longer treatment times. In addition, when rescanning is applied on its own, large differences between volumetric and layered rescanning have been observed as a function of increasing number of re-scans. However, once gating and rescanning is combined, HI to within 2% of the static plan could be achieved in the clinical target volume, with only moderately prolonged treatment times, irrespective of the rescanning strategy used. Moreover, these results are independent of the motion surrogate used. In conclusion, our results suggest image guided beam gating, combined with rescanning, is a feasible, effective and efficient motion mitigation approach for PBS-based liver tumour treatments.