Incremental willingness to pay: a theoretical and empirical exposition

Applications of willingness to pay (WTP) have shown the difficultly to discriminate between various options. This reflects the problem of embedding in both its specific sense, of options being nested within one another, and its more-general sense, whereby respondents cannot discriminate between close substitutes or between more-disparate rivals for the same budget. Furthermore, high proportions of reversals between WTP-value and simple preference based rankings of options are often highlighted. Although an incremental WTP approach was devised to encourage more differentiated answers and a higher degree of consistency among respondents, a theoretical basis for this approach has not been elucidated, and there is little evidence to show that this approach might indeed achieve greater consistency between explicit and implicit rankings inferred from WTP values.We address both these issues. Following our theoretical exposition, standard and incremental approaches were compared with explicit ranking in a study assessing preferences for different French emergency care services. 280 persons, representative of the French adult population, were interviewed. Half received the incremental version, the other half the standard version. Results suggest that the incremental approach provides a ranking of options fully in line with explicit ranking. The standard approach was reasonably consistent with explicit ranking but proved unable to differentiate between the five most preferred providers, as predicted by theory. Our findings suggest that the incremental approach provides results which can be used in priority-setting contexts

Ontogeny of aerial righting and wing flapping in juvenile birds

Mechanisms of aerial righting in juvenile Chukar Partridge (Alectoris chukar) were studied from hatching through 14 days post hatching (dph). Asymmetric movements of the wings were used from 1 to 8 dph to effect progressively more successful righting behaviour via body roll. Following 8 dph, wing motions transitioned to bilaterally symmetric flapping that yielded aerial righting via nose down pitch, along with substantial increases in vertical force production during descent. Ontogenetically, the use of such wing motions to effect aerial righting precedes both symmetric flapping and a previously documented behaviour in chukar (i.e., wing assisted incline running) hypothesized to be relevant to incipient flight evolution in birds. These findings highlight the importance of asymmetric wing activation and controlled aerial manoeuvres during bird development, and are potentially relevant to understanding the origins of avian flight

Shifts in stability and control effectiveness during evolution of Paraves support aerial maneuvering hypotheses for flight origins

The capacity for aerial maneuvering shaped the evolution of flying animals. Here we evaluate consequences of aviaian morphology for aerial performance (1,2) by quantifying static stability and control effectiveness of physical models (3) for numerous taxa sampled from within the lineage leading to birds (Paraves, 4). Results of aerodynamic testing are mapped phylogenetically (5-9) to examine how maneuvering characteristics correlate with tail shortening, fore- and hindwing elaboration, and other morphological features (10). In the evolution of the Avialae we observe shifts from static stability to inherently unstable aerial planforms; control effectiveness also migrated from tails to the forewings. These shifts suggest that some degree of aerodynamic control and and capacity for maneuvering preceded the evolution of strong power stroke. The timing of shifts also suggests some features normally considered in light of development of a power stroke may play important roles in control.Comment: 12 pages, 6 figures, 1 supplemental figures and 5 supplemental table

How does priority setting for resource allocation happen in commissioning dental services in a nationally led, regionally delivered system: a qualitative study using semistructured interviews with NHS England dental commissioners

Objectives: To understand approaches to priority setting for healthcare service resource allocation at an operational level in a nationally commissioned but regionally delivered service. Design: Qualitative study using semistructured interviews and a Framework analysis. Setting: National Health Service dentistry commissioning teams within subregional offices in England. Participants: All 31 individuals holding the relevant role (dental lead commissioner in subregional offices) were approached directly and from this 14 participants were recruited, with 12 interviews completed. Both male and female genders and all regions were represented in the final sample. Results: Three major themes arose. First, 'Methods of priority setting and barriers to explicit approaches' was a common theme, specifically identifying the main methods as: perpetuating historical allocations, pressure from politicians and clinicians and use of needs assessments while barriers were time and skill deficits, a lack of national guidance and an inflexible contracting arrangements stopping resource allocation. Second, 'Relationships with key stakeholders and advisors' were discussed, showing the important nature of relationships with clinical advisors but variation in the quality of these relationships was noted. Finally, 'Tensions between national and local responsibilities' were illustrated, where there was confusion about where power and autonomy lay. Conclusions: Commissioners recognised a need for resource allocation but relied on clinical advice and needs assessment in order to set priorities. More explicit priority setting was prevented by structure of the commissioning system and standard national contracts with providers. Further research is required to embed and simplify adoption of tools to aid priority setting

Srs2 removes deadly recombination intermediates independently of its interaction with SUMO-modified PCNA

Saccharomyces cerevisiae Srs2 helicase plays at least two distinct functions. One is to prevent recombinational repair through its recruitment by sumoylated Proliferating Cell Nuclear Antigen (PCNA), evidenced in postreplication-repair deficient cells, and a second one is to eliminate potentially lethal intermediates formed by recombination proteins. Both actions are believed to involve the capacity of Srs2 to displace Rad51 upon translocation on single-stranded DNA (ssDNA), though a role of its helicase activity may be important to remove some toxic recombination structures. Here, we described two new mutants, srs2R1 and srs2R3, that have lost the ability to hinder recombinational repair in postreplication-repair mutants, but are still able to remove toxic recombination structures. Although the mutants present very similar phenotypes, the mutated proteins are differently affected in their biochemical activities. Srs2R1 has lost its capacity to interact with sumoylated PCNA while the biochemical activities of Srs2R3 are attenuated (ATPase, helicase, DNA binding and ability to displace Rad51 from ssDNA). In addition, crossover (CO) frequencies are increased in both mutants. The different roles of Srs2, in relation to its eventual recruitment by sumoylated PCNA, are discussed

In vivo visualization of age-related differences in the locus coeruleus.

The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer-weighted images to investigate the relationship between LC CR and age in cognitively normal healthy adults (N = 605, age range 18-88 years). Study participants were part of the Cambridge Centre for Ageing and Neuroscience-an open-access, population-based data set. We found a quadratic relationship between LC CR and age, the peak occurring around 60 years, with no differences between males and females. Subregional analyses revealed that age-related decline in LC CR was confined to the rostral portion of the LC. Older adults showed greater variance in overall LC CR than younger adults, and the functional and clinical implications of these observed age-related differences require further investigation. Visualization of the LC in this study may inform how future scanning parameters can be optimized, and provides insight into how LC integrity changes across the life span

Stable Patterns of Gene Expression Regulating Carbohydrate Metabolism Determined by Geographic Ancestry

Background: Individuals of African descent in the United States suffer disproportionately from diseases with a metabolic etiology (obesity, metabolic syndrome, and diabetes), and from the pathological consequences of these disorders (hypertension and cardiovascular disease). Methodology/Principal Findings: Using a combination of genetic/genomic and bioinformatics approaches, we identified a large number of genes that were both differentially expressed between American subjects self-identified to be of either African or European ancestry and that also contained single nucleotide polymorphisms that distinguish distantly related ancestral populations. Several of these genes control the metabolism of simple carbohydrates and are direct targets for the SREBP1, a metabolic transcription factor also differentially expressed between our study populations. Conclusions/Significance: These data support the concept of stable patterns of gene transcription unique to a geographic ancestral lineage. Differences in expression of several carbohydrate metabolism genes suggest both genetic and transcriptional mechanisms contribute to these patterns and may play a role in exacerbating the disproportionate levels o

Controlled Release of Stem Cell Secretome Attenuates Inflammatory Response against Implanted Biomaterials

Inflammatory response against implanted biomaterials impairs their functional integration and induces medical complications in the host's body. To suppress such immune responses, one approach is the administration of multiple drugs to halt inflammatory pathways. This challenges patient's adherence and can cause additional complications such as infection. Alternatively, biologics that regulate multiple inflammatory pathways are attractive agents in addressing the implants immune complications. Secretome of mesenchymal stromal cells (MSCs) is a multipotent biologic, regulating the homeostasis of lymphocytes and leukocytes. Here, it is reported that alginate microcapsules loaded with processed conditioned media (pCM-Alg) reduces the infiltration and/or expression of CD68+ macrophages likely through the controlled release of pCM. In vitro cultures revealed that alginate can dose dependently induce macrophages to secrete TNFα, IL-6, IL-1β, and GM-CSF. Addition of pCM to the cultures attenuates the secretion of TNFα (p = 0.023) and IL-6 (p < 0.0001) by alginate or lipopolysaccharide (LPS) stimulations. Mechanistically, pCM suppressed the NfκB pathway activation of macrophages in response to LPS (p < 0.0001) in vitro and cathepsin activity (p = 0.005) in response to alginate in vivo. These observations suggest the efficacy of using MSC-derived secretome to prevent or delay the host rejection of implants