Backward Reachability of Array-based Systems by SMT solving: Termination and Invariant Synthesis

The safety of infinite state systems can be checked by a backward reachability procedure. For certain classes of systems, it is possible to prove the termination of the procedure and hence conclude the decidability of the safety problem. Although backward reachability is property-directed, it can unnecessarily explore (large) portions of the state space of a system which are not required to verify the safety property under consideration. To avoid this, invariants can be used to dramatically prune the search space. Indeed, the problem is to guess such appropriate invariants. In this paper, we present a fully declarative and symbolic approach to the mechanization of backward reachability of infinite state systems manipulating arrays by Satisfiability Modulo Theories solving. Theories are used to specify the topology and the data manipulated by the system. We identify sufficient conditions on the theories to ensure the termination of backward reachability and we show the completeness of a method for invariant synthesis (obtained as the dual of backward reachability), again, under suitable hypotheses on the theories. We also present a pragmatic approach to interleave invariant synthesis and backward reachability so that a fix-point for the set of backward reachable states is more easily obtained. Finally, we discuss heuristics that allow us to derive an implementation of the techniques in the model checker MCMT, showing remarkable speed-ups on a significant set of safety problems extracted from a variety of sources.Comment: Accepted for publication in Logical Methods in Computer Scienc

Edge influence on vegetation at natural and anthropogenic edges of boreal forests in Canada and Fennoscandia

Although anthropogenic edges are an important consequence of timber harvesting, edges due to natural disturbances or landscape heterogeneity are also common. Forest edges have been well studied in temperate and tropical forests, but less so in less productive, disturbance-adapted boreal forests. We synthesized data on forest vegetation at edges of boreal forests and compared edge influence among edge types (fire, cut, lake/wetland; old vs. young), forest types (broadleaf vs. coniferous) and geographic regions. Our objectives were to quantify vegetation responses at edges of all types and to compare the strength and extent of edge influence among different types of edges and forests. Research was conducted using the same general sampling design in Alberta, Ontario and Quebec in Canada, and in Sweden and Finland. We conducted a meta-analysis for a variety of response variables including forest structure, deadwood abundance, regeneration, understorey abundance and diversity, and non-vascular plant cover. We also determined the magnitude and distance of edge influence (DEI) using randomization tests. Some edge responses (lower tree basal area, tree canopy and bryophyte cover; more logs; higher regeneration) were significant overall across studies. Edge influence on ground vegetation in boreal forests was generally weak, not very extensive (DEI usually < 20 m) and decreased with time. We found more extensive edge influence at natural edges, at younger edges and in broadleaf forests. The comparison among regions revealed weaker edge influence in Fennoscandian forests. Synthesis. Edges created by forest harvesting do not appear to have as strong, extensive or persistent influence on vegetation in boreal as in tropical or temperate forested ecosystems. We attribute this apparent resistance to shorter canopy heights, inherent heterogeneity in boreal forests and their adaptation to frequent natural disturbance. Nevertheless, notable differences between forest structure responses to natural (fire) and anthropogenic (cut) edges raise concerns about biodiversity implications of extensive creation of anthropogenic edges. By highlighting universal responses to edge influence in boreal forests that are significant irrespective of edge or forest type, and those which vary by edge type, we provide a context for the conservation of boreal forests. Edges created by forest harvesting do not appear to have as strong, extensive or persistent influence on vegetation in boreal as in tropical or temperate forested ecosystems. We attribute this apparent resistance to shorter canopy heights, inherent heterogeneity in boreal forests and their adaptation to frequent natural disturbance. Nevertheless, notable differences between forest structure responses to natural (fire) and anthropogenic (cut) edges raise concerns about biodiversity implications of extensive creation of anthropogenic edges. By highlighting universal responses to edge influence in boreal forests that are significant irrespective of edge or forest type, and those which vary by edge type, we provide a context for the conservation of boreal forests

Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications

Summary: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries. Purpose The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications. Methods: Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year. Results: Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was −2.7 (SD 0.89; median −2.7 [interquartile range, −3.2, −2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study. Conclusions POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care

Roadless and Low-Traffic Areas as Conservation Targets in Europe

With increasing road encroachment, habitat fragmentation by transport infrastructures has been a serious threat for European biodiversity. Areas with no roads or little traffic (“roadless and low-traffic areas”) represent relatively undisturbed natural habitats and functioning ecosystems. They provide many benefits for biodiversity and human societies (e.g., landscape connectivity, barrier against pests and invasions, ecosystem services). Roadless and low-traffic areas, with a lower level of anthropogenic disturbances, are of special relevance in Europe because of their rarity and, in the context of climate change, because of their contribution to higher resilience and buffering capacity within landscape ecosystems. An analysis of European legal instruments illustrates that, although most laws aimed at protecting targets which are inherent to fragmentation, like connectivity, ecosystem processes or integrity, roadless areas are widely neglected as a legal target. A case study in Germany underlines this finding. Although the Natura 2000 network covers a significant proportion of the country (16%), Natura 2000 sites are highly fragmented and most low-traffic areas (75%) lie unprotected outside this network. This proportion is even higher for the old Federal States (western Germany), where only 20% of the low-traffic areas are protected. We propose that the few remaining roadless and low-traffic areas in Europe should be an important focus of conservation efforts; they should be urgently inventoried, included more explicitly in the law and accounted for in transport and urban planning. Considering them as complementary conservation targets would represent a concrete step towards the strengthening and adaptation of the Natura 2000 network to climate change

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis