The impact of prolonged lower limb ischemia on amputation, mortality, and functional status: the FRIENDS registry.

BACKGROUND Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival. METHODS The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year. RESULTS A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI. CONCLUSIONS For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

There is more than "more is up": Hand and foot responses reverse the vertical association of number magnitudes

Recent research in cognitive sciences shows a growing interest in spatial-numerical associations. The horizontal SNARC (spatial-numerical association of response codes) effect is defined by faster left-sided responses to small numbers and faster right-sided responses to large numbers in a parity judgment task. In this study we investigated whether there is also a SNARC effect for upper and lower responses. The grounded cognition approach suggests that the universal experience of "more is up" serves as a robust frame of reference for vertical number representation. In line with this view, lower hand responses to small numbers were faster than to large numbers (Experiment 1). Interestingly, the vertical SNARC effect reversed when the lower responses were given by foot instead of the hand (Experiments 2, 3, and 4). We found faster upper (hand) responses to small numbers and faster lower (foot) responses to large numbers. Additional experiments showed that spatial factors cannot account for the reversal of the vertical SNARC effect (Experiments 4 and 5). Our results question the view of "more is up" as a robust frame of reference for spatial-numerical associations. We discuss our results within a hierarchical framework of numerical cognition and point to a possible link between effectors and number representation.

The association of childhood trauma and personality disorder with adult chronic depression. A cross-sectional study in depressed outpatients

Objective: Chronic depression has often been associated with childhood trauma. There may, however, be an interaction between personality pathology, childhood trauma, and chronic depression. This interaction has not yet been studied. Method: This retrospective analysis is based on 279 patients contacted for a randomized trial in an outpatient psychotherapy center over a period of 18 months from 2010 to 2012. Current diagnoses of a personality disorder and presence of chronic depression were systematically assessed using the Structured Clinical Interview for DSM-IV. Retrospective reports of childhood trauma were collected using the short form of the Childhood Trauma Questionnaire (CTQ-SF). DSM-IV–defined chronic depression was the primary outcome. The association between chronic depression, childhood trauma, and personality disorders was analyzed using correlations. Variables that had at least a small effect on correlation analysis were entered into a series of logistic regression analyses to determine the predictors of chronic depression and the moderating effect of childhood trauma. Results: The presence of avoidant personality disorder, but no CTQ-SF scale, was associated with the chronicity of depression (odds ratio [OR] = 2.20, P = .015). The emotional abuse subscale of the CTQ-SF did, however, correlate with avoidant personality disorder (OR = 1.15, P = .000). The level of emotional abuse had a moderating effect on the effect of avoidant personality disorder on the presence of chronic depression (OR = 1.08, P = .004). Patients who did not suffer from avoidant personality disorder had a decreased rate of chronic depression if they retrospectively reported more severe levels of emotional abuse (18.9% vs 39.7%, respectively). Conclusions: The presence of avoidant personality pathology may interact with the effect of childhood trauma in the development of chronic depression. This has to be confirmed in a prospective study.

Innovative Agricultural Approaches of Promoting Food Security in Eritrea: Trends, Challenges and Opportunities for Growth: Proceedings of the Workshop of the Association of Eritreans in Agricultural Sciences (AEAS)

Eritrea is a Sahel country in terms of climate, and rainfall is low and highly variable. Shortage of food is thus a recurrent problem, and food security one of the key issues in development. The present publication presents the results of a nationwide workshop organised in 2006 in Asmara, Eritrea, by the Association of Eritreans in Agricultural Sciences (AEAS). The workshop was attended by over 200 participants from government administration, academia, development circles including NGOs and UN organisations. Specifically, the present publication deals with themes such as biotechnology, non-wood forest products, spate irrigation, the role of women relating to food security, and institutional and organisational aspects of food security. It also contains a chapter with policy recommendations, as well as an extensive summary of the main findings (paper abstracts) in Tigrinya.

Report of a European Society of Cardiology-European Association of Percutaneous Cardiovascular Interventions task force on the evaluation of coronary stents in Europe: executive summary.

The evaluation for European Union market approval of coronary stents falls under the Medical Device Directive that was adopted in 1993. Specific requirements for the assessment of coronary stents are laid out in supplementary advisory documents. In response to a call by the European Commission to make recommendations for a revision of the advisory document on the evaluation of coronary stents (Appendix 1 of MEDDEV 2.7.1), the European Society of Cardiology (ESC) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) established a Task Force to develop an expert advisory report. As basis for its report, the ESC-EAPCI Task Force reviewed existing processes, established a comprehensive list of all coronary drug-eluting stents that have received a CE mark to date, and undertook a systematic review of the literature of all published randomized clinical trials evaluating clinical and angiographic outcomes of coronary artery stents between 2002 and 2013. Based on these data, the TF provided recommendations to inform a new regulatory process for coronary stents. The main recommendations of the task force include implementation of a standardized non-clinical assessment of stents and a novel clinical evaluation pathway for market approval. The two-stage clinical evaluation plan includes recommendation for an initial pre-market trial with objective performance criteria (OPC) benchmarking using invasive imaging follow-up leading to conditional CE-mark approval and a subsequent mandatory, large-scale randomized trial with clinical endpoint evaluation leading to unconditional CE-mark. The data analysis from the systematic review of the Task Force may provide a basis for determination of OPC for use in future studies. This paper represents an executive summary of the Task Force's report.

Complex geomorphologic assemblage of terrains in association with the banded terrain in Hellas basin, Mars

Hellas basin acts as a major sink for the southern highlands of Mars and is likely to have recorded several episodes of sedimentation and erosion. The north-western part of the basin displays a potentially unique Amazonian landscape domain in the deepest part of Hellas, called “banded terrain”, which is a deposit characterized by an alternation of narrow band shapes and inter-bands displaying a sinuous and relatively smooth surface texture suggesting a viscous flow origin. Here we use high-resolution (HiRISE and CTX) images to assess the geomorphological interaction of the banded terrain with the surrounding geomorphologic domains in the NW interior of Hellas to gain a better understanding of the geological evolution of the region as a whole. Our analysis reveals that the banded terrain is associated with six geomorphologic domains: a central plateau named Alpheus Colles, plain deposits (P1 and P2), reticulate (RT1 and RT2) and honeycomb terrains. Based on the analysis of the geomorphology of these domains and their cross-cutting relationships, we show that no widespread deposition post-dates the formation of the banded terrain, which implies that this domain is the youngest and latest deposit of the interior of Hellas. Therefore, the level of geologic activity in the NW Hellas during the Amazonian appears to have been relatively low and restricted to modification of the landscape through mechanical weathering, aeolian and periglacial processes. Thermophysical data and cross-cutting relationships support hypotheses of modification of the honeycomb terrain via vertical rise of diapirs such as ice diapirism, and the formation of the plain deposits through deposition and remobilization of an ice-rich mantle deposit. Finally, the observed gradual transition between honeycomb and banded terrain suggests that the banded terrain may have covered a larger area of the NW interior of Hellas in the past than previously thought. This has implications on the understanding of the evolution of the deepest part of Hellas.

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

OBJECTIVES Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients. METHODS Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analyzed by sandwich-type immunoassays and genotyping, respectively, and correlated with development of heavy Candida colonization (corrected colonization index (CCI) ≥0.4) and occurrence of IAC during a 4-week period. RESULTS Within 4 weeks after inclusion a CCI ≥0.4 and IAC was observed in 47% and 38% of patients respectively. Neither serum levels of MBL, ficolin-1, -2, -3, MASP-2 or collectin liver 1 nor MBL2 genotypes were associated with a CCI ≥0.4. Similarly, none of the analyzed proteins was found to be associated with IAC with the exception of lower MBL levels (HR 0.74, p = 0.02) at study entry. However, there was no association of MBL deficiency (<0.5 μg/ml), MBL2 haplo- or genotypes with IAC. CONCLUSION Lectin pathway protein levels and MBL2 genotype investigated in this study were not associated with heavy Candida colonization or IAC in a cohort of high-risk ICU patients.

Development of a Novel Green Fluorescent Protein-Based Binding Assay to Study the Association of Plakins with Intermediate Filament Proteins.

Protein-protein interactions are fundamental for most biological processes, such as the formation of cellular structures and enzymatic complexes or in signaling pathways. The identification and characterization of protein-protein interactions are therefore essential for understanding the mechanisms and regulation of biological systems. The organization and dynamics of the cytoskeleton, as well as its anchorage to specific sites in the plasma membrane and organelles, are regulated by the plakins. These structurally related proteins anchor different cytoskeletal networks to each other and/or to other cellular structures. The association of several plakins with intermediate filaments (IFs) is critical for maintenance of the cytoarchitecture. Pathogenic mutations in the genes encoding different plakins can lead to dramatic manifestations, occurring principally in the skin, striated muscle, and/or nervous system, due to cytoskeletal disorganization resulting in abnormal cell fragility. Nevertheless, it is still unclear how plakins bind to IFs, although some general rules are slowly emerging. We here describe in detail a recently developed protein-protein fluorescence binding assay, based on the production of recombinant proteins tagged with green fluorescent protein (GFP) and their use as fluid-phase fluorescent ligands on immobilized IF proteins. Using this method, we have been able to assess the ability of C-terminal regions of GFP-tagged plakin proteins to bind to distinct IF proteins and IF domains. This simple and sensitive technique, which is expected to facilitate further studies in this area, can also be potentially employed for any kind of protein-protein interaction studies.

Intracellular membrane association of the N-terminal domain of classical swine fever virus NS4B determines viral genome replication and virulence.

Classical swine fever virus (CSFV) causes a highly contagious disease in pigs that can range from a severe haemorrhagic fever to a nearly unapparent disease, depending on the virulence of the virus strain. Little is known about the viral molecular determinants of CSFV virulence. The nonstructural protein NS4B is essential for viral replication. However, the roles of CSFV NS4B in viral genome replication and pathogenesis have not yet been elucidated. NS4B of the GPE-  vaccine strain and of the highly virulent Eystrup strain differ by a total of seven amino acid residues, two of which are located in the predicted trans-membrane domains of NS4B and were described previously to relate to virulence, and five residues clustering in the N-terminal part. In the present study, we examined the potential role of these five amino acids in modulating genome replication and determining pathogenicity in pigs. A chimeric low virulent GPE- -derived virus carrying the complete Eystrup NS4B showed enhanced pathogenicity in pigs. The in vitro replication efficiency of the NS4B chimeric GPE-  replicon was significantly higher than that of the replicon carrying only the two Eystrup-specific amino acids in NS4B. In silico and in vitro data suggest that the N-terminal part of NS4B forms an amphipathic α-helix structure. The N-terminal NS4B with these five amino acid residues is associated with the intracellular membranes. Taken together, this is the first gain-of-function study showing that the N-terminal domain of NS4B can determine CSFV genome replication in cell culture and viral pathogenicity in pigs.

Promoting palliative care in the community: production of the primary palliative care toolkit by the European Association of Palliative Care Taskforce in primary palliative care

BACKGROUND A multidisciplinary European Association of Palliative Care Taskforce was established to scope the extent of and learn what facilitates and hinders the development of palliative care in the community across Europe. AIM To document the barriers and facilitators for palliative care in the community and to produce a resource toolkit that palliative care specialists, primary care health professionals or policymakers, service developers, educationalists and national groups more generally could use to facilitate the development of palliative care in their own country. DESIGN (1) A survey instrument was sent to general practitioners with knowledge of palliative care services in the community in a diverse sample of European countries. We also conducted an international systematic review of tools used to identify people for palliative care in the community. (2) A draft toolkit was then constructed suggesting how individual countries might best address these issues, and an online survey was then set up for general practitioners and specialists to make comments. Iterations of the toolkit were then presented at international palliative care and primary care conferences. RESULTS Being unable to identify appropriate patients for palliative care in the community was a major barrier internationally. The systematic review identified tools that might be used to help address this. Various facilitators such as national strategies were identified. A primary palliative care toolkit has been produced and refined, together with associated guidance. CONCLUSION Many barriers and facilitators were identified. The primary palliative care toolkit can help community-based palliative care services to be established nationally.