Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Exploring synergies and trade-offs among the sustainable development goals: collective action and adaptive capacity in marginal mountainous areas of India

Global environmental change (GEC) threatens to undermine the sustainable development goals (SDGs). Smallholders in marginal mountainous areas (MMA) are particularly vulnerable due to precarious livelihoods in challenging environments. Acting collectively can enable and constrain the ability of smallholders to adapt to GEC. The objectives of this paper are: (i) identify collective actions in four MMA of the central Indian Himalaya Region, each with differing institutional contexts; (ii) assess the adaptive capacity of each village by measuring livelihood capital assets, diversity, and sustainable land management practices. Engaging with adaptive capacity and collective action literatures, we identify three broad approaches to adaptive capacity relating to the SDGs: natural hazard mitigation (SDG 13), social vulnerability (SDG 1, 2 and 5), and social–ecological resilience (SDG 15). We then develop a conceptual framework to understand the institutional context and identify SDG synergies and trade-offs. Adopting a mixed method approach, we analyse the relationships between collective action and the adaptive capacity of each village, the sites where apparent trade-offs and synergies among SDGs occur. Results illustrate each village has unique socio-environmental characteristics, implying distinct development challenges, vulnerabilities and adaptive capacities exist. Subsequently, specific SDG synergies and trade-offs occur even within MMA, and it is therefore crucial that institutions facilitate locally appropriate collective actions in order to achieve the SDGs. We suggest that co-production in the identification, prioritisation and potential solutions to the distinct challenges facing MMA can increase understandings of the specific dynamics and feedbacks necessary to achieve the SDGs in the context of GEC

European Electricity Market Reforms: Any Signs of Efficiency Improvements?

This paper investigates whether European electricity market refirms have induced any changes infirm efficiency either through productive, allocative or dynamic efficiency improve- ments. In particular, this ex-post analysis looks closely at productivity e ects of changing industry structure, ownership structure and regulation with respect to barriers to entry and access to wholesale and retail markets. Based on the Europeanfirm-level data for the period 1996-2007, the results indicate sluggish productivity improvements of European electricityfirms due to refirms implemented in the last decade. In particular, productivity gains are associated with high-productivityfirms close to the technology frontier, while no signi cant impact is found for the laggards. Looking from a dynamic perspective, it seems that the clos- est are thefirms to the frontier the more they are able to improve productivity in response to liberalization e orts stimulating competition

In-hospital care, complications, and 4-month mortality following a hip or proximal femur fracture: the Spanish registry of osteoporotic femur fractures prospective cohort study

Summary We have characterised 997 hip fracture patients from a representative 45 Spanish hospitals, and followed them up prospectively for up to 4 months. Despite suboptimal surgical delays (average 59.1 hours), in-hospital mortality was lower than in Northern European cohorts. The secondary fracture prevention gap is unacceptably high at 85%. Purpose To characterise inpatient care, complications, and 4-month mortality following a hip or proximal femur fracture in Spain. Methods Design: prospective cohort study. Consecutive sample of patients ≥ 50 years old admitted in a representative 45 hospitals for a hip or proximal femur fragility fracture, from June 2014 to June 2016 and followed up for 4 months post-fracture. Patient characteristics, site of fracture, in-patient care (including secondary fracture prevention) and complications, and 4-month mortality are described. Results A total of 997 subjects (765 women) of mean (standard deviation) age 83.6 (8.4) years were included. Previous history of fracture/s (36.9%) and falls (43%) were common, and 10-year FRAX-estimated major and hip fracture risks were 15.2% (9.0%) and 8.5% (7.6%) respectively. Inter-trochanteric (44.6%) and displaced intra-capsular (28.0%) were the most common fracture sites, and fixation with short intramedullary nail (38.6%) with spinal anaesthesia (75.5%) the most common procedures. Surgery and rehabilitation were initiated within a mean 59.1 (56.7) and 61.9 (55.1) hours respectively, and average length of stay was 11.5 (9.3) days. Antithrombotic and antibiotic prophylaxis were given to 99.8% and 98.2% respectively, whilst only 12.4% received secondary fracture prevention at discharge. Common complications included delirium (36.1 %) and kidney failure (14.1%), with in-hospital and 4-month mortality of 2.1% and 11% respectively. Conclusions Despite suboptimal surgical delay, post-hip fracture mortality is low in Spanish hospitals. The secondary fracture prevention gap is unacceptably high at > 85%, in spite of virtually universal anti-thrombotic and antibiotic prophylaxis

Measuring the neighbourhood using UK benefits data: a multilevel analysis of mental health status

Background: Evidence from multilevel research investigating whether the places where people live influence their mental health remains inconclusive. The objectives of this study are to derive small area-level, or contextual, measures of the local social environment using benefits data from the Department of Work and Pensions (DWP) and to investigate whether (1) the mental health status of individuals is associated with contextual measures of low income, economic inactivity, and disability, after adjusting for personal risk factors for poor mental health, (2) the associations between mental health and context vary significantly between different population sub-groups, and (3) to compare the effect of the contextual benefits measures with the Townsend area deprivation score. Methods: Data from the Welsh Health Survey 1998 were analysed in Normal response multilevel models of 24,975 individuals aged 17 to 74 years living within 833 wards and 22 unitary authorities in Wales. The mental health outcome measure was the Mental Health Inventory (MHI-5) of the Short Form 36 health status questionnaire. The benefits data available were the means tested Income Support and Income-based Job Seekers Allowance, and the non-means tested Incapacity Benefit, Severe Disablement Allowance, Disability Living Allowance and Attendance Allowance. Indirectly age-standardised census ward ratios were calculated to model as the contextual measures. Results: Each contextual variable was significantly associated with individual mental health after adjusting for individual risk factors, so that living in a ward with high levels of claimants was associated with worse mental health. The non-means tested benefits that were proxy measures of economic inactivity from permanent sickness or disability showed stronger associations with individual mental health than the means tested benefits and the Townsend score. All contextual effects were significantly stronger in people who were economically inactive and unavailable for work. Conclusion: This study provides evidence for substantive contextual effects on mental health, and in particular the importance of small-area levels of economic inactivity and disability. DWP benefits data offer a more specific measure of local neighbourhood than generic deprivation indices and offer a starting point to hypothesise possible causal pathways to individual mental health status

Candida albicans AGE3, the Ortholog of the S. cerevisiae ARF-GAP-Encoding Gene GCS1, Is Required for Hyphal Growth and Drug Resistance

BACKGROUND: Hyphal growth and multidrug resistance of C. albicans are important features for virulence and antifungal therapy of this pathogenic fungus. METHODOLOGY/PRINCIPAL FINDINGS: Here we show by phenotypic complementation analysis that the C. albicans gene AGE3 is the functional ortholog of the yeast ARF-GAP-encoding gene GCS1. The finding that the gene is required for efficient endocytosis points to an important functional role of Age3p in endosomal compartments. Most C. albicans age3Delta mutant cells which grew as cell clusters under yeast growth conditions showed defects in filamentation under different hyphal growth conditions and were almost completely disabled for invasive filamentous growth. Under hyphal growth conditions only a fraction of age3Delta cells shows a wild-type-like polarization pattern of the actin cytoskeleton and lipid rafts. Moreover, age3Delta cells were highly susceptible to several unrelated toxic compounds including antifungal azole drugs. Irrespective of the AGE3 genotype, C-terminal fusions of GFP to the drug efflux pumps Cdr1p and Mdr1p were predominantly localized in the plasma membrane. Moreover, the plasma membranes of wild-type and age3Delta mutant cells contained similar amounts of Cdr1p, Cdr2p and Mdr1p. CONCLUSIONS/SIGNIFICANCE: The results indicate that the defect in sustaining filament elongation is probably caused by the failure of age3Delta cells to polarize the actin cytoskeleton and possibly of inefficient endocytosis. The high susceptibility of age3Delta cells to azoles is not caused by inefficient transport of efflux pumps to the cell membrane. A possible role of a vacuolar defect of age3Delta cells in drug susceptibility is proposed and discussed. In conclusion, our study shows that the ARF-GAP Age3p is required for hyphal growth which is an important virulence factor of C. albicans and essential for detoxification of azole drugs which are routinely used for antifungal therapy. Thus, it represents a promising antifungal drug target

There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

Höhn S, Hallmann A. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator. BMC Biology. 2011;9(1): 89.Background: Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results: In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions: Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator

Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus

Pooled analysis of who surgical safety checklist use and mortality after emergency laparotomy

Background: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods: In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results: Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89⋅6 per cent) compared with that in countries with a middle (753 of 1242, 60⋅6 per cent; odds ratio (OR) 0⋅17, 95 per cent c.i. 0⋅14 to 0⋅21, P < 0⋅001) or low (363 of 860, 42⋅2 percent; OR 0⋅08, 0⋅07 to 0⋅10, P < 0⋅001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9⋅4 (95 per cent c.i. −11⋅9 to −6⋅9) per cent; P < 0⋅001), but the relationship was reversed in low-HDI countries (+12⋅1 (+7⋅0 to +17⋅3) per cent; P < 0⋅001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0⋅60, 0⋅50 to 0⋅73; P < 0⋅001). The greatest absolute benefit was seen for emergency surgery in low-and middle-HDI countries. Conclusion: Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries