Interface vulnerability and knowledge of the subjunctive/indicative distinction with negated epistemic predicates in L2 Spanish.

Much recent research in SLA is guided by the hypothesis of L2 interface vulnerability (see Sorace 2005). This study contributes to this general project by examining the acquisition of two classes of subjunctive complement clauses in L2 Spanish: subjunctive complements of volitional predicates (purely syntactic) and subjunctive vs. indicative complements with negated epistemic matrix predicates, where the mood distinction is discourse dependent (thus involving the syntax-discourse interface). We provide an analysis of the volitional subjunctive in English and Spanish, suggesting that English learners of L2 Spanish need to access the functional projection Mood P and an uninterpretable modal feature on the Force head available to them from their formal English register grammar, and simultaneously must unacquire the structure of English for-to clauses. For negated epistemic predicates, our analysis maintains that they need to revalue the modal feature on the Force head from uninterpretable to interpretable, within the L2 grammar.With others (e.g. Borgonovo & Prévost 2003; Borgonovo, Bruhn de Garavito & Prévost 2005) and in line with Sorace's (2000, 2003, 2005) notion of interface vulnerability, we maintain that the latter case is more difficult for L2 learners, which is borne out in the data we present. However, the data also show that the indicative/subjunctive distinction with negated epistemics can be acquired by advanced stages of acquisition, questioning the notion of obligatory residual optionality for all properties which require the integration of syntactic and discourse information.

Livelihoods and Vulnerability in the Arid and Semi-Arid Lands of Southern Africa: Exploring the links between ecosystem services and poverty alleviation

This book sets out the findings of research conducted into the links between ecosystem services and poverty alleviation in Southern Africa. It follows from extensive primary research conducted in the region, as well as intensive engagement with researchers, policy-makers and relevant institutions in several countries in southern Africa, as part of the Ecosystem Services and Poverty Alleviation Programme led by DFI, NERC and ESRC.

Flood inundation dynamics and socioeconomic vulnerability under environmental change

Floods are a major threat to human existence and historically have both caused the collapse of civilizations and forced the emergence of new cultures. The physical processes of flooding are complex. Increased population, climate variability, change in catchment and channel management, modified landuse and land cover, and natural change of floodplains and river channels all lead to changes in flood dynamics, and as a direct or indirect consequence, social welfare of humans. Section 5.16.1 explores the risks and benefits brought about by floods and reviews the responses of floods and floodplains to climate and landuse change. Section 5.08.2 reviews the existing modeling tools, and the top–down and bottom–up modeling frameworks that are used to assess impacts on future floods. Section 5.08.3 discusses changing flood risk and socioeconomic vulnerability based on current trends in emerging or developing countries and presents an alternative paradigm as a pathway to resilience. Section 5.08.4 concludes the chapter by stating a portfolio of integrated concepts, measures, and avant-garde thinking that would be required to sustainably manage future flood risk.

Assessing the impact on chronic disease of incorporating the societal cost of greenhouse gases into the price of food: an econometric and comparative risk assessment modelling study

Objectives To model the impact on chronic disease of a tax on UK food and drink that internalises the wider costs to society of greenhouse gas (GHG) emissions and to estimate the potential revenue. Design An econometric and comparative risk assessment modelling study. Setting The UK. Participants The UK adult population. Interventions Two tax scenarios are modelled: (A) a tax of £2.72/tonne carbon dioxide equivalents (tCO2e)/100 g product applied to all food and drink groups with above average GHG emissions. (B) As with scenario (A) but food groups with emissions below average are subsidised to create a tax neutral scenario. Outcome measures Primary outcomes are change in UK population mortality from chronic diseases following the implementation of each taxation strategy, the change in the UK GHG emissions and the predicted revenue. Secondary outcomes are the changes to the micronutrient composition of the UK diet. Results Scenario (A) results in 7770 (95% credible intervals 7150 to 8390) deaths averted and a reduction in GHG emissions of 18 683 (14 665to 22 889) ktCO2e/year. Estimated annual revenue is £2.02 (£1.98 to £2.06) billion. Scenario (B) results in 2685 (1966 to 3402) extra deaths and a reduction in GHG emissions of 15 228 (11 245to 19 492) ktCO2e/year. Conclusions Incorporating the societal cost of GHG into the price of foods could save 7770 lives in the UK each year, reduce food-related GHG emissions and generate substantial tax revenue. The revenue neutral scenario (B) demonstrates that sustainability and health goals are not always aligned. Future work should focus on investigating the health impact by population subgroup and on designing fiscal strategies to promote both sustainable and healthy diets.

Examining vulnerability to involuntary memories in schizophrenia comorbid with post-traumatic stress disorder

The current study explored whether individuals diagnosed with schizophrenia and a high level of PTSD symptoms experience more frequent neutral intrusive memories than individuals diagnosed with schizophrenia with low level PTSD symptoms. Results supported a vulnerability to neutral intrusive memories within the comorbid group, which did not seem to be related to psychotic symptom severity. It is possible that a subgroup of psychotic individuals’ process information in a manner that make them susceptible to frequent intrusive memories, characteristic of a PTSD presentation. A longitudinal study is required to specify the development of this vulnerability so as to inform future interventions.

Data-driven treatment selection for seamless phase II/III trials incorporating early-outcome data

Seamless phase II/III clinical trials are conducted in two stages with treatment selection at the first stage. In the first stage, patients are randomized to a control or one of k > 1 experimental treatments. At the end of this stage, interim data are analysed, and a decision is made concerning which experimental treatment should continue to the second stage. If the primary endpoint is observable only after some period of follow-up, at the interim analysis data may be available on some early outcome on a larger number of patients than those for whom the primary endpoint is available. These early endpoint data can thus be used for treatment selection. For two previously proposed approaches, the power has been shown to be greater for one or other method depending on the true treatment effects and correlations. We propose a new approach that builds on the previously proposed approaches and uses data available at the interim analysis to estimate these parameters and then, on the basis of these estimates, chooses the treatment selection method with the highest probability of correctly selecting the most effective treatment. This method is shown to perform well compared with the two previously described methods for a wide range of true parameter values. In most cases, the performance of the new method is either similar to or, in some cases, better than either of the two previously proposed methods.

Incorporating semiotics into fuzzy logic to enhance Clinical Decision Support Systems

In order to enhance the quality of care, healthcare organisations are increasingly resorting to clinical decision support systems (CDSSs), which provide physicians with appropriate health care decisions or recommendations. However, how to explicitly represent the diverse vague medical knowledge and effectively reason in the decision-making process are still problems we are confronted. In this paper, we incorporate semiotics into fuzzy logic to enhance CDSSs with the aim of providing both the abilities of describing medical domain concepts contextually and reasoning with vague knowledge. A semiotically inspired fuzzy CDSSs framework is presented, based on which the vague knowledge representation and reasoning process are demonstrated.

Self-assembly of a Model Peptide incorporating a Hexa-Histidine sequence attached to an Oligo-Alanine sequence, and binding to Gold NTA/Nickel nanoparticles

Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexahistidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac’s), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

HIV-related stigma, asset inheritance and chronic poverty: vulnerability and resilience of widows and caregiving children and youth in Tanzania and Uganda

This paper develops a framework of risk and protective factors to conceptualise the relationship between HIV-related stigma, asset inheritance and chronic poverty among widows and caregiving children and youth in eastern Africa. Analysis of two qualitative studies with 85 participants in rural and urban areas of Tanzania and Uganda reveals that gendered and generational inequalities and stigmatisation sometimes led to property grabbing and chronic poverty. Human and social capital and preventative measures however may help widows and caregiving young people in HIV-affected households to safeguard land and other assets, within a wider supportive environment that seeks to tackle structural inequalities.

Incorporating toxicokinetics into an individual-based model for more realistic pesticide exposure estimates: A case study of the wood mouse

The potential risk of agricultural pesticides to mammals typically depends on internal concentrations within individuals, and these are determined by the amount ingested and by absorption, distribution, metabolism, and excretion (ADME). Pesticide residues ingested depend, amongst other things, on individual spatial choices which determine how much and when feeding sites and areas of pesticide application overlap, and can be calculated using individual-based models (IBMs). Internal concentrations can be calculated using toxicokinetic (TK) models, which are quantitative representations of ADME processes. Here we provide a population model for the wood mouse (Apodemus sylvaticus) in which TK submodels were incorporated into an IBM representation of individuals making choices about where to feed. This allows us to estimate the contribution of individual spatial choice and TK processes to risk. We compared the risk predicted by four IBMs: (i) “AllExposed-NonTK”: assuming no spatial choice so all mice have 100% exposure, no TK, (ii) “AllExposed-TK”: identical to (i) except that the TK processes are included where individuals vary because they have different temporal patterns of ingestion in the IBM, (iii) “Spatial-NonTK”: individual spatial choice, no TK, and (iv) “Spatial-TK”: individual spatial choice and with TK. The TK parameters for hypothetical pesticides used in this study were selected such that a conventional risk assessment would fail. Exposures were standardised using risk quotients (RQ; exposure divided by LD50 or LC50). We found that for the exposed sub-population including either spatial choice or TK reduced the RQ by 37–85%, and for the total population the reduction was 37–94%. However spatial choice and TK together had little further effect in reducing RQ. The reasons for this are that when the proportion of time spent in treated crop (PT) approaches 1, TK processes dominate and spatial choice has very little effect, and conversely if PT is small spatial choice dominates and TK makes little contribution to exposure reduction. The latter situation means that a short time spent in the pesticide-treated field mimics exposure from a small gavage dose, but TK only makes a substantial difference when the dose was consumed over a longer period. We concluded that a combined TK-IBM is most likely to bring added value to the risk assessment process when the temporal pattern of feeding, time spent in exposed area and TK parameters are at an intermediate level; for instance wood mice in foliar spray scenarios spending more time in crop fields because of better plant cover.

Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers’ disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly “nanodisc” structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/ Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

A comparison of methods for treatment selection in seamless phase II/III clinical trials incorporating information on short-term endpoints

In an adaptive seamless phase II/III clinical trial interim analysis, data are used for treatment selection, enabling resources to be focused on comparison of more effective treatment(s) with a control. In this paper, we compare two methods recently proposed to enable use of short-term endpoint data for decision-making at the interim analysis. The comparison focuses on the power and the probability of correctly identifying the most promising treatment. We show that the choice of method depends on how well short-term data predict the best treatment, which may be measured by the correlation between treatment effects on short- and long-term endpoints.

Self-assembly of a dual functional bioactive peptide amphiphile incorporating both matrix metalloprotease substrate and cell adhesion motifs

We describe a bioactive lipopeptide that combines the capacity to promote the adhesion and subsequent self-detachment of live cells, using template-cell-environment feedback interactions. This self-assembling peptide amphiphile comprises a diene-containing hexadecyl lipid chain (C16e) linked to a matrix metalloprotease-cleavable sequence, Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln, and contiguous with a cell-attachment and signalling motif, Arg-Gly-Asp-Ser. Biophysical characterisation revealed that the PA self-assembles into 3 nm diameter spherical micelles above a critical aggregation concentration (cac). In addition, when used in solution at 5–150 nM (well below the cac), the PA is capable of forming film coatings that provide a stable surface for human corneal fibroblasts to attach and grow. Furthermore, these coatings were demonstrated to be sensitive to metalloproteases expressed endogenously by the attached cells, and consequently to elicit the controlled detachment of cells without compromising their viability. As such, this material constitutes a novel class of multi-functional coating for both fundamental and clinical applications in tissue engineering.