IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial

BACKGROUND The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate "patient-centric" outcomes of functional limb preservation, mobility and quality of life (QoL). METHODS/DESIGN IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. DISCUSSION This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are discussed. IN.PACT DEEP is a milestone, prospective, randomized, robust, independent core lab-adjudicated CLI trial that will evaluate the role of a new infrapopliteal revascularization technology, the IA-DEB, compared to PTA. It will assess the overall impact on infrapopliteal artery patency, limb salvage, wound healing, pain control, QoL, and patient mobility. The 1-year results of the adjudicated co-primary and secondary endpoints will be available in 2014. TRIAL REGISTRATION NCT00941733

The craniosacral progression of muscle development influences the emergence of neuromuscular junction alterations in a severe murine model for spinal muscular atrophy.

AIMS As 4-day-old mice of the severe spinal muscular atrophy (SMA) model (dying at 5-8 days) display pronounced neuromuscular changes in the diaphragm but not the soleus muscle, we wanted to gain more insight into the relationship between muscle development and the emergence of pathological changes and additionally to analyse intercostal muscles which are affected in human SMA. METHODS Structures of muscle fibres and neuromuscular junctions (NMJs) of the diaphragm, intercostal and calf muscles of prenatal (E21) and postnatal (P0 and P4) healthy and SMA mice were analysed by light and transmission electron microscopy. NMJ innervation was studied by whole mount immunofluorescence in diaphragms of P4 mice. RESULTS During this period, the investigated muscles still show a significant neck-to-tail developmental gradient. The diaphragm and calf muscles are most and least advanced, respectively, with respect to muscle fibre fusion and differentiation. The number and depth of subsynaptic folds increases, and perisynaptic Schwann cells (PSCs) acquire a basal lamina on their outer surface. Subsynaptic folds are connected to an extensive network of tubules and beaded caveolae, reminiscent of the T system in adult muscle. Interestingly, intercostal muscles from P4 SMA mice show weaker pathological involvement (that is, vacuolization of PSCs and perineurial cells) than those previously described by us for the diaphragm, whereas calf muscles show no pathological changes. CONCLUSION SMA-related alterations appear to occur only when the muscles have reached a certain developmental maturity. Moreover, glial cells, in particular PSCs, play an important role in SMA pathogenesis.

Thermal Conditions at the Bed of the Laurentide Ice Sheet in Maine During Deglaciation: Implications for Esker Formation

The University of Maine Ice Sheet Model was used to study basal conditions during retreat of the Laurentide ice sheet in Maine. Within 150 km of the margin, basal melt rates average similar to 5 mm a(-1) during retreat. They decline over the next 100km, so areas of frozen bed develop in northern Maine during retreat. By integrating the melt rate over the drainage area typically subtended by an esker, we obtained a discharge at the margin of similar to 1.2 m(3) s(-1). While such a discharge could have moved the material in the Katahdin esker, it was likely too low to build the esker in the time available. Additional water from the glacier surface was required. Temperature gradients in the basal ice increase rapidly with distance from the margin. By conducting upward into the ice all of the additional viscous heat produced by any perturbation that increases the depth of flow in a flat conduit in a distributed drainage system, these gradients inhibit the formation of sharply arched conduits in which an esker can form. This may explain why eskers commonly seem to form near the margin and are typically segmented, with later segments overlapping onto earlier ones.

Tidal Flexure of Jakobshavns Glacier, West Greenland

Jakobshavns Glacier, a floating outlet glacier on the West Greenland coast, was surveyed during July 1976. The vertical displacements of targets along two profiles perpendicular to the fjord wall bounding the north margin of the glacier were analyzed to determine the effect of flexure caused by tidal oscillations within the fjord. An analysis based on the assumption that vertical displacements of the glacier reflected pure elastic bending yielded the conclusion that the effective thickness of the ice (i.e., the thickness which remained unaffected by surface and basal cracking and which behaved as a continuum) was ∼160 m 2.6 km upglacier from the calving front and ∼110 m 0.6 km from the calving front. An analysis based on the more realistic assumption that observed bending reflected elastic and viscoplastic deformation yielded the conclusion that the average effective thickness of the ice was 316 ± 74 m (∼40% of the estimated 800-m total thickness) 2.6 km from the calving front and 160 ± 48 m (∼21% of the estimated 750-m total) 0.6 km from the calving front. A constitutive relationship appropriate for hard glide during flexure was used.

Tertiary Minette and Melanephelinite Dikes, Wasatch Plateau, Utah - Records of Mantle Heterogeneities and Changing Tectonics

A swarm of minette and melanephelinite dikes is exposed over 2500 km2 in and near the Wasatch Plateau, central Utah, along the western margin of the Colorado Plateaus in the transition zone with the Basin and Range province. To date, 110 vertical dikes in 25 dike sets have been recognized. Strikes shift from about N80-degrees-W for 24 Ma dikes, to about N60-degrees-W for 18 Ma, to due north for 8-7 m.y. These orientations are consistent with a shift from east-west Oligocene compression associated with subduction to east-west late Miocene crustal extension. Minettes are the most common rock type; mica-rich minette and mica-bearing melanephelinite occurs in 24 Ma dikes, whereas more ordinary minette is found in 8-7 Ma dikes. One melanephelinite dike is 18 Ma. These mafic alkaline rocks are transitional to one another in modal and major element composition but have distinctive trace element patterns and isotopic compositions; they appear to have crystallized from primitive magmas. Major, trace element, and Nd-Sr isotopic data indicate that melanephelinite, which has similarities to ocean island basalt, was derived from small degree melts of mantle with a chondritic Sm/Nd ratio probably located in the asthenosphere, but it is difficult to rule out a lithospheric source. In contrast, mica-bearing rocks (mica melanephelinite and both types of minette) are more potassic and have trace element patterns with strong Nb-Ta depletions and Sr-Nd isotopic compositions caused by involvement with a component from heterogeneously enriched lithospheric mantle with long-term enrichment of Rb or light rare earth elements (REE) (epsilon Nd as low as - 15 in minette). Light REE enrichment must have occurred anciently in the mid-Proterozoic when the lithosphere was formed and is not a result of Cenozoic subduction processes. After about 25 Ma, foundering of the subducting Farallon plate may have triggered upwelling of warm asthenospheric mantle to the base of the lithosphere. Melanephelinite magma may have separated from the asthenosphere and, while rising through the lithosphere, provided heat for lithospheric magma generation. Varying degrees of interaction between melanephelinite and small potassic melt fractions derived from the lithospheric mantle can explain the gradational character of the melanephelinite to minette suite.

Surgical anatomy of the feline sacroiliac joint for lag screw fixation of sacroiliac fracture-luxation

Twenty-eight feline pelves (56 hemipelves) were examined in order to identify the location for optimal sacroiliac screw placement in sacroiliac fracture-luxation repair. A drill hole was started on the median plane of the hemipelvis in the centre of the body of the first sacral segment until it penetrated the lateral cortex of the ilial wing, thus providing optimal drill hole placement. The position of the drill hole on the articular surface of the sacral wing and on the lateral surface of the ilial wing was measured. The distance of the drill hole from the cranial margin of the sacral wing was 51% of sacral wing length, just cranial to the crescent shaped hyaline cartilage. The distance from the dorsal margin was 47% of sacral wing height. The drill bit direction has to be adjusted to the cranio-caudal inclination (range 10° to 29°) and dorso-ventral inclination (range 2° to 25°) of the sacral wing. A notch in the cranial edge of the sacral wing was present, with variable position, in 34% of the specimens and is consequently not a useful landmark for sacroiliac screw placement. The drill hole on the lateral surface of the ilium was located in craniocaudal direction at a distance of 69% of sacral tuber length, measured from the cranial dorsal iliac spine. The dorso-ventral position of the drill hole was at a distance of 52% of ilial wing height measured from the sacral tuber. The ventral gluteal line, present in 93% of the cases, is a useful landmark to locate optimal screw hole position on the ilial wing.

More Than Charged Base Loss — Revisiting the Fragmentation of Highly Charged Oligonucleotides

Tandem mass spectrometry is a well-established analytical tool for rapid and reliable characterization of oligonucleotides (ONs) and their gas-phase dissociation channels. The fragmentation mechanisms of native and modified nucleic acids upon different mass spectrometric activation techniques have been studied extensively, resulting in a comprehensive catalogue of backbone fragments. In this study, the fragmentation behavior of highly charged oligodeoxynucleotides (ODNs) comprising up to 15 nucleobases was investigated. It was found that ODNs exhibiting a charge level (ratio of the actual to the total possible charge) of 100% follow significantly altered dissociation pathways compared with low or medium charge levels if a terminal pyrimidine base (3' or 5') is present. The corresponding product ion spectra gave evidence for the extensive loss of a cyanate anion (NCO–), which frequently coincided with the abstraction of water from the 3'- and 5'-end in the presence of a 3'- and 5'-terminal pyrimidine nucleobase, respectively. Subsequent fragmentation of the MNCO– ion by MS3 revealed a so far unreported consecutive excision of a metaphosphate (PO3–)-ion for the investigated sequences. Introduction of a phosphorothioate group allowed pinpointing of PO3– loss to the ultimate phosphate group. Several dissociation mechanisms for the release of NCO– and a metaphosphate ion were proposed and the validity of each mechanism was evaluated by the analysis of backbone- or sugar modified ONs.

Extent and distribution of calcification of both the aortic annulus and the left ventricular outflow tract predict aortic regurgitation after transcatheter aortic valve replacement

Aims: We sought to analyse local distribution of aortic annulus and left ventricular outflow tract (LVOT) calcification in patients undergoing transcatheter aortic valve replacement (TAVR) and its impact on aortic regurgitation (AR) immediately after device placement. Methods and results: A group of 177 patients with severe aortic stenosis undergoing multislice computed tomography of the aortic root followed by TAVR were enrolled in this single-centre study. Annular and LVOT calcifications were assessed per cusp using a semi-quantitative grading system (0: none; 1 [mild]: small, non-protruding calcifications; 2 [moderate]: protruding [>1 mm] or extensive [>50% of cusp sector] calcifications; 3 [severe]: protruding and extensive calcifications). Any calcification of the annulus or LVOT was present in 107 (61%) and 63 (36%) patients, respectively. Prevalence of annulus/LVOT calcifications in the left coronary cusp was 42% and 25%, respectively, in the non-coronary cusp 28% and 13%, in the right coronary cusp 13% and 5%. AR grade 2 to 4 assessed by the method of Sellers immediately after TAVR device implantation was observed in 55 patients (31%). Multivariate regression analysis revealed that the overall annulus calcification (OR [95% CI] 1.48 [1.10-2.00]; p=0.0106), the overall LVOT calcification (1.93 [1.26-2.96]; p=0.0026), any moderate or severe LVOT calcification (5.37 [1.52-18.99]; p=0.0092), and asymmetric LVOT calcification were independent predictors of AR. Conclusions: Calcifications of the aortic annulus and LVOT are frequent in patients undergoing TAVR, and both the distribution and the severity of calcifications appear to be independent predictors of aortic regurgitation after device implantation. - See more at: http://www.pcronline.com/eurointervention/77th_issue/126/#sthash.Hzodgju5.dpuf

The role of human-induced fire and sweet chestnut (Castanea sativa Mill.) cultivation on the long-term landscape dynamics of the southern Swiss Alps

Changes in fire occurrence during the last decades in the southern Swiss Alps make knowledge on fire history essential to understand future evolution of the ecosystem composition and functioning. In this context, palaeoecology provides useful insights into processes operating at decadal-to-millennial time scales, such as the response of plant communities to intensified fire disturbances during periods of cultural change. We provide a high-resolution macroscopic charcoal and pollen series from Guèr, a well-dated peat sequence at mid-elevation (832 m.a.s.l.) in southern Switzerland, where the presence of local settlements is documented since the late Bronze Age and the Iron Age. Quantitative fire reconstruction shows that fire activity sharply increased from the Neolithic period (1–3 episodes/1000 year) to the late Bronze and Iron Age (7–9 episodes/1000 year), leading to extensive clearance of the former mixed deciduous forest (Alnus glutinosa, Betula, deciduous Quercus). The increase in anthropogenic pollen indicators (e.g. Cerealia-type, Plantago lanceolata) together with macroscopic charcoal suggests anthropogenic rather than climatic forcing as the main cause of the observed vegetation shift. Fire and controlled burning were extensively used during the late Roman Times and early Middle Ages to promote the introduction and establishment of chestnut (Castanea sativa) stands, which provided an important wood and food supply. Fire occurrence declined markedly (from 9 to 5–6 episodes/1000 year) during late Middle Ages because of fire suppression, biomass removal by human population, and landscape fragmentation. Land-abandonment during the last decades allowed forest to partly re-expand (mainly Alnus glutinosa, Betula) and fire frequency to increase.

Role of Urbanization, Land-Use Diversity, and Livestock Intensification in Zoonotic Emerging Infectious Diseases

Emerging infectious diseases (EIDs) continue to significantly threaten human and animal health. While there has been some progress in identifying underlying proximal driving forces and causal mechanisms of disease emergence, the role of distal factors is most poorly understood. This article focuses on analyzing the statistical association between highly pathogenic avian influenza (HPAI) H5N1 and urbanization, land-use diversity and poultry intensification. A special form of the urban transition—peri-urbanization—was hypothesized as being associated with ‘hot-spots’ of disease emergence. Novel metrics were used to characterize these distal risk factors. Our models, which combined these newly proposed risk factors with previously known natural and human risk factors, had a far higher predictive performance compared to published models for the first two epidemiological waves in Viet Nam. We found that when relevant risk factors are taken into account, urbanization is generally not a significant independent risk factor. However, urbanization spatially combines other risk factors leading to peri-urban places being the most likely ‘hot-spots’. The work highlights that peri-urban areas have highest levels of chicken density, duck and geese flock size diversity, fraction of land under rice, fraction of land under aquaculture compared to rural and urban areas. Land-use diversity, which has previously never been studied in the context of HPAI H5N1, was found to be a significant risk factor. Places where intensive and extensive forms of poultry production are collocated were found to be at greater risk.

Aorto-bronchial and aorto-pulmonary fistulation after thoracic endovascular aortic repair: an analysis from the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To learn upon incidence, underlying mechanisms and effectiveness of treatment strategies in patients with central airway and pulmonary parenchymal aorto-bronchial fistulation after thoracic endovascular aortic repair (TEVAR). METHODS Analysis of an international multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2012 with a total caseload of 4680 TEVAR procedures (14 centres). RESULTS Twenty-six patients with a median age of 70 years (interquartile range: 60-77) (35% female) were identified. The incidence of either central airway (aorto-bronchial) or pulmonary parenchymal (aorto-pulmonary) fistulation (ABPF) in the entire cohort after TEVAR in the study period was 0.56% (central airway 58%, peripheral parenchymal 42%). Atherosclerotic aneurysm formation was the leading indication for TEVAR in 15 patients (58%). The incidence of primary endoleaks after initial TEVAR was n = 10 (38%), of these 80% were either type I or type III endoleaks. Fourteen patients (54%) developed central left bronchial tree lesions, 11 patients (42%) pulmonary parenchymal lesions and 1 patient (4%) developed a tracheal lesion. The recognized mechanism of ABPF was external compression of the bronchial tree in 13 patients (50%), the majority being due to endoleak formation, further ischaemia due to extensive coverage of bronchial feeding arteries in 3 patients (12%). Inflammation and graft erosion accounted for 4 patients (30%) each. Cumulative survival during the entire study period was 39%. Among deaths, 71% were attributed to ABPF. There was no difference in survival in patients having either central airway or pulmonary parenchymal ABPF (33 vs 45%, log-rank P = 0.55). Survival with a radical surgical approach was significantly better when compared with any other treatment strategy in terms of overall survival (63 vs 32% and 63 vs 21% at 1 and 2 years, respectively), as well as in terms of fistula-related survival (63 vs 43% and 63 vs 43% at 1 and 2 years, respectively). CONCLUSIONS ABPF is a rare but highly lethal complication after TEVAR. The leading mechanism behind ABPF seems to be a continuing external compression of either the bronchial tree or left upper lobe parenchyma. In this setting, persisting or newly developing endoleak formation seems to play a crucial role. Prognosis does not differ in patients with central airway or pulmonary parenchymal fistulation. Radical bronchial or pulmonary parenchymal repair in combination with stent graft removal and aortic reconstruction seems to be the most durable treatment strategy.

Human and ecological risk assessment of a crop protection chemical: a case study with the azole fungicide epoxiconazole.

Conventional risk assessments for crop protection chemicals compare the potential for causing toxicity (hazard identification) to anticipated exposure. New regulatory approaches have been proposed that would exclude exposure assessment and just focus on hazard identification based on endocrine disruption. This review comprises a critical analysis of hazard, focusing on the relative sensitivity of endocrine and non-endocrine endpoints, using a class of crop protection chemicals, the azole fungicides. These were selected because they are widely used on important crops (e.g. grains) and thereby can contact target and non-target plants and enter the food chain of humans and wildlife. Inhibition of lanosterol 14α-demethylase (CYP51) mediates the antifungal effect. Inhibition of other CYPs, such as aromatase (CYP19), can lead to numerous toxicological effects, which are also evident from high dose human exposures to therapeutic azoles. Because of its widespread use and substantial database, epoxiconazole was selected as a representative azole fungicide. Our critical analysis concluded that anticipated human exposure to epoxiconazole would yield a margin of safety of at least three orders of magnitude for reproductive effects observed in laboratory rodent studies that are postulated to be endocrine-driven (i.e. fetal resorptions). The most sensitive ecological species is the aquatic plant Lemna (duckweed), for which the margin of safety is less protective than for human health. For humans and wildlife, endocrine disruption is not the most sensitive endpoint. It is concluded that conventional risk assessment, considering anticipated exposure levels, will be protective of both human and ecological health. Although the toxic mechanisms of other azole compounds may be similar, large differences in potency will require a case-by-case risk assessment.

Are shrubs really a sign of declining ecosystem function? Disentangling the myths and truths of woody encroachment in Australia

Since European settlement, there has been a dramatic increase in the density, cover and distribution of woody plants in former grassland and open woodland. There is a widespread belief that shrub encroachment is synonymous with declines in ecosystem functions, and often it is associated with landscape degradation or desertification. Indeed, this decline in ecosystem functioning is considered to be driven largely by the presence of the shrubs themselves. This prevailing paradigm has been the basis for an extensive program of shrub removal, based on the view that it is necessary to reinstate the original open woodland or grassland structure from which shrublands are thought to have been derived. We review existing scientific evidence, particularly focussed on eastern Australia, to question the notion that shrub encroachment leads to declines in ecosystem functions. We then summarise this scientific evidence into two conceptual models aimed at optimising landscape management to maximise the services provided by shrub-encroached areas. The first model seeks to reconcile the apparent conflicts between the patch- and landscape-level effects of shrubs. The second model identifies the ecosystem services derived from different stages of shrub encroachment. We also examined six ecosystem services provided by shrublands (biodiversity, soil C, hydrology, nutrient provision, grass growth and soil fertility) by using published and unpublished data. We demonstrated the following: (1) shrub effects on ecosystems are strongly scale-, species- and environment-dependent and, therefore, no standardised management should be applied to every case; (2) overgrazing dampens the generally positive effect of shrubs, leading to the misleading relationship between encroachment and degradation; (3) woody encroachment per se does not hinder any of the functions or services described above, rather it enhances many of them; (4) no single shrub-encroachment state (including grasslands without shrubs) will maximise all services; rather, the provision of ecosystem goods and services by shrublands requires a mixture of different states; and (5) there has been little rigorous assessment of the long-term effectiveness of removal and no evidence that this improves land condition in most cases. Our review provides the basis for an improved, scientifically based understanding and management of shrublands, so as to balance the competing goals of providing functional habitats, maintaining soil processes and sustaining pastoral livelihoods.

Recurring slope lineae in equatorial regions of Mars

The presence of liquid water is a requirement of habitability on a planet. Possible indicators of liquid surface water on Mars include intermittent flow-like features observed on sloping terrains. These recurring slope lineae are narrow, dark markings on steep slopes that appear and incrementally lengthen during warm seasons on low-albedo surfaces. The lineae fade in cooler seasons and recur over multiple Mars years. Recurring slope lineae were initially reported to appear and lengthen at mid-latitudes in the late southern spring and summer and are more common on equator-facing slopes where and when the peak surface temperatures are higher. Here we report extensive activity of recurring slope lineae in equatorial regions of Mars, particularly in the deep canyons of Valles Marineris, from analysis of data acquired by the Mars Reconnaissance Orbiter. We observe the lineae to be most active in seasons when the slopes often face the sun. Expected peak temperatures suggest that activity may not depend solely on temperature. Although the origin of the recurring slope lineae remains an open question, our observations are consistent with intermittent flow of briny water. Such an origin suggests surprisingly abundant liquid water in some near-surface equatorial regions of Mars.

Enhancing Food Sovereignty and Food Security through the Revitalization of Indigenous Knowledge: Experiences from the Bolivian Andes

Endogenous development is defined as development that values primarily locally available resources and the way people organized themselves for that purpose. It is a dynamic and evolving concept that also embraces innovations and complementation from other than endogenous sources of knowledge; however, only as far as they are based on mutual respect and the recognition of cultural and socioeconomic self-determination of each of the parties involved. Experiences that have been systematized in the context of the BioAndes Program are demonstrating that enhancing food security and food sovereignty on the basis of endogenous development can be best achieved by applying a ‘biocultural’ perspective: This means to promote and support actions that are simultaneously valuing biological (fauna, flora, soils, or agrobiodiversity) and sociocultural resources (forms of social organization, local knowledge and skills, norms, and the related worldviews). In Bolivia, that is one of the Latin-American countries with the highest levels of poverty (79% of the rural population) and undernourishment (22% of the total population), the Program BioAndes promotes food sovereignty and food security by revitalizing the knowledge of Andean indigenous people and strengthening their livelihood strategies. This starts by recognizing that Andean people have developed complex strategies to constantly adapt to highly diverse and changing socioenvironmental conditions. These strategies are characterized by organizing the communities, land use and livelihoods along a vertical gradient of the available eco-climatic zones; the resulting agricultural systems are evolving around the own sociocultural values of reciprocity and mutual cooperation, giving thus access to an extensive variety of food, fiber and energy sources. As the influences of markets, competition or individualization are increasingly affecting the life in the communities, people became aware of the need to find a new balance between endogenous and exogenous forms of knowledge. In this context, BioAndes starts by recognizing the wealth and potentials of local practices and aims to integrate its actions into the ongoing endogenous processes of innovation and adaptation. In order to avoid external impositions and biases, the program intervenes on the basis of a dialogue between exogenous, mainly scientific, and indigenous forms of knowledge. The paper presents an analysis of the strengths and weaknesses of enhancing endogenous development through a dialogue between scientific and indigenous knowledge by specifically focusing on its effects on food sovereignty and food security in three ‘biocultural’ rural areas of the Bolivian highlands. The paper shows how the dialogue between different forms of knowledge evolved alongside the following project activities: 1) recuperation and renovation of local seeds and crop varieties (potato – Solanum spp., quinoa – Chenopodium quinoa, cañahua – Chenopodium pallidicaule); 2) support for the elaboration of community-based norms and regulations for governing access and distribution of non-timber forest products, such as medicinal, fodder, and construction plants; 3) revitalization of ethnoveterinary knowledge for sheep and llama breeding; 4) improvement of local knowledge about the transformation of food products (sheep-cheese, lacayote – Cucurbita sp. - jam, dried llama meat, fours of cañahua and other Andean crops). The implementation of these activities fostered the community-based livelihoods of indigenous people by complementing them with carefully and jointly designed innovations based on internal and external sources of knowledge and resources. Through this process, the epistemological and ontological basis that underlies local practices was made visible. On this basis, local and external actors started to jointly define a renewed concept of food security and food sovereignty that, while oriented in the notions of well being according to a collectively re-crafted world view, was incorporating external contributions as well. Enabling and hindering factors, actors and conditions of these processes are discussed in the paper.