Stimulus Threat and Exposure Context Modulate the Effect of Mere Exposure on Approach Behaviors

Mere-exposure (ME) research has found that initially neutral objects made familiar are preferred relative to novel objects. Recent work extends these preference judgments into the behavioral domain by illustrating that mere exposure prompts approachoriented behavior toward familiar stimuli. However, no investigations have examined the effect of mere exposure on approach-oriented behavior toward threatening stimuli. The current work examines this issue and also explores how exposure context interacts with stimulus threat to influence behavioral tendencies. In two experiments participants were presented with both mere-exposed and novel stimuli and approach speed was assessed. In the first experiment, when stimulus threat was presented in a homogeneous format (i.e., participants viewed exclusively neutral or threatening stimuli), ME potentiated approach behaviors for both neutral and threatening stimuli. However, in the second experiment, in which stimulus threat was presented in a heterogeneous fashion (i.e., participants viewed both neutral and threatening stimuli), mere exposure facilitated approach only for initially neutral stimuli. These results suggest that ME effects on approach behaviors are highly context sensitive and depend on both stimulus valence and exposure context. Further implications of these findings for the ME literature are discussed

Pramlintide in the Management of Obesity

Obesity is a common problem that can lead to numerous comorbid conditions, including Type 2 diabetes. Currently, there are few pharmacologic options available to help obese patients lose weight. Pramlintide is an injectable, amylin analogue that is indicated in patients with Type 1 and Type 2 diabetes for use in conjunction with insulin to improve glycemic control. In addition to helping patients decrease hemoglobin A1c levels, pramlintide has also been shown to minimize weight gain, especially in patients with Type 2 diabetes. Studies have been conducted in various patient types, including those patients without diabetes, and the drug tends to have a positive effect on weight loss. It appears that the drug is well tolerated in patients without diabetes; however, current studies have been conducted in small patient populations. Additional research needs to be carried out to determine if the drug is a viable option for obese patients who have failed to respond to other weight loss products

A Novel, Contactless, Portable “Spot-Check” Device Accurately Measures Respiratory Rate

Respiratory rate (RR) is an important vital sign used in the assessment of acutely ill patients. It is also used as to predict serious deterioration in a patient's clinical condition. Convenient electronic devices exist for measurement of pulse, blood pressure, oxygen saturation and temperature. Although devices which measure RR exist, none has entered everyday clinical practice. We developed a contactless portable respiratory rate monitor (CPRM) and evaluated the agreement in respiratory rate measurements between existing methods and our new device. The CPRM uses thermal anemometry to measure breath signals during inspiration and expiration. RR data were collected from 52 healthy adult volunteers using respiratory inductance plethysmography (RIP) bands (established contact method), visual counting of chest movements (established non-contact method) and the CPRM (new method), simultaneously. Two differently shaped funnel attachments were evaluated for each volunteer. Data showed good agreement between measurements from the CPRM and the gold standard RIP, with intra-class correlation coefficient (ICC): 0.836, mean difference 0.46 and 95% limits of agreement of -5.90 to 6.83. When separate air inlet funnels of the CPRM were analysed, stronger agreement was seen with an elliptical air inlet; ICC 0.908, mean difference 0.37 with 95% limits of agreement -4.35 to 5.08. A contactless device for accurately and quickly measuring respiratory rate will be an important triage tool in the clinical assessment of patients. More testing is needed to explore the reasons for outlying measurements and to evaluate in the clinical setting

Legume based plant mixtures for delivery of multiple ecosystem services: An overview of benefits

As costs for mineral fertilizers rise, legume-based leys are recognised as a potential alternative nitrogen source for crops. Here we demonstrate that including species-rich legume-based leys in the rotation helps to maximize synergies between agricultural productivity and other ecosystem services. By using functionally diverse plant species mixtures these services can be optimised and fine-tuned to regional and farm-specific needs. Field experiments run over three years at multiple locations showed that the stability of ley performance was greater in multi-species mixtures than in legume monocultures. In addition, mixing different legume species in the ley helps to suppress both early and late weeds. Further, combining complementary phenologies of different legume species extended forage availability for key pollinator species. Finally, widening the range of legume species increases opportunities to build short term leys into rotations on conventional farms via cover cropping or undersowing

Clinical and MRI responses to etanercept in early non-radiographic axial spondyloarthritis : 48-week results from the EMBARK study

Objective: To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here. Results: 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48. Conclusions: Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks

Metal worker’s lung: spatial association with Mycobacterium avium

Background Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak. Objectives After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone. Methods Custom-quantitative PCR assays, microscopy and phylogenetic analyses were performed on blinded MWF samples to quantify microbial burden and identify potential aetiological agents of HP in metal workers. Measurements and main results MWF from machines fed by a central sump, but not those with an isolated supply, was contaminated by mycobacteria. The factory sump and a single linked machine at the centre of the outbreak zone, known to be the workstation of the index cases, had very high levels of detectable organisms. Phylogenetic placement of mycobacterial taxonomic marker genes generated from these samples indicated that the contaminating organisms were closely related to Mycobacterium avium. Conclusions We describe, for the first time, a close spatial relationship between the abundance of a mycobacterium-like organism, most probably M. avium, and a localised outbreak of MWF-associated HP. The further development of sequence-based analytic techniques should assist in the prevention of this important occupational disease

Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

BACKGROUND AIMS: In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid-the UDCA response-accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets. METHODS: We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response ("responders"), 16 PBC patients with inadequate UDCA response ("nonresponders"), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes ("modules") associated with response status and the most highly connected genes ("hub genes") within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation ("latent factors") across all peripheral blood mononuclear cell subsets. RESULTS: Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q<0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated-but also kept in check-in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders. CONCLUSIONS: We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response

Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive destruction of intrahepatic bile ducts. The strongest genetic association is with HLA-DQA1*04:01, but at least three additional independent HLA haplotypes contribute to susceptibility. We used dense single nucleotide polymorphism (SNP) data in 2861 PBC cases and 8514 controls to impute classical HLA alleles and amino acid polymorphisms using state-of-the-art methodologies. We then demonstrated through stepwise regression that association in the HLA region can be largely explained by variation at five separate amino acid positions. Three-dimensional modelling of protein structures and calculation of electrostatic potentials for the implicated HLA alleles/amino acid substitutions demonstrated a correlation between the electrostatic potential of pocket P6 in HLA-DP molecules and the HLA-DPB1 alleles/amino acid substitutions conferring PBC susceptibility/protection, highlighting potential new avenues for future functional investigation

Weeds in Organic Fertility-Building Leys: Aspects of Species Richness and Weed Management

Legume-based leys (perennial sod crops) are an important component of fertility management in organic rotations in many parts of Europe. Despite their importance, however, relatively little is known about how these leys affect weed communities or how the specific composition of leys may contribute to weed management. To determine whether the choice of plant species in the ley affects weeds, we conducted replicated field trials at six locations in the UK over 24 months, measuring weed cover and biomass in plots sown with monocultures of 12 legume and 4 grass species, and in plots sown with a mixture of 10 legume species and 4 grass species. Additionally, we monitored weed communities in leys on 21 organic farms across the UK either sown with a mixture of the project species or the farmers’ own species mix. In total, 63 weed species were found on the farms, with the annuals Stellaria media, Sonchus arvensis, and Veronica persica being the most frequent species in the first year after establishment of the ley, while Stellaria media and the two perennials Ranunculus repens and Taraxacum officinale dominated the weed spectrum in the second year. Our study shows that organic leys constitute an important element of farm biodiversity. In both replicated and on-farm trials, weed cover and species richness were significantly lower in the second year than in the first, owing to lower presence of annual weeds in year two. In monocultures, meadow pea (Lathyrus pratensis) was a poor competitor against weeds, and a significant increase in the proportion of weed biomass was observed over time, due to poor recovery of meadow pea after mowing. For red clover (Trifolium pratense), we observed the lowest proportion of weed biomass in total biomass among the tested legume species. Crop biomass and weed biomass were negatively correlated across species. Residuals from the linear regression between crop biomass and weed biomass indicated that at similar levels of crop biomass, grasses had lower weed levels than legumes. We conclude that choice of crop species is an important tool for weed management in leys

Stakeholder Theory and Marketing: Moving from a Firm-Centric to a Societal Perspective

This essay is inspired by the ideas and research examined in the special section on “Stakeholder Marketing” of the Journal of Public Policy & Marketing in 2010. The authors argue that stakeholder marketing is slowly coalescing with the broader thinking that has occurred in the stakeholder management and ethics literature streams during the past quarter century. However, the predominant view of stakeholders that many marketers advocate is still primarily pragmatic and company centric. The position advanced herein is that stronger forms of stakeholder marketing that reflect more normative, macro/societal, and network-focused orientations are necessary. The authors briefly explain and justify these characteristics in the context of the growing “prosociety” and “proenvironment” perspectives—orientations that are also in keeping with the public policy focus of this journal. Under the “hard form” of stakeholder theory, which the authors endorse, marketing managers must realize that serving stakeholders sometimes requires sacrificing maximum profits to mitigate outcomes that would inflict major damage on other stakeholders, especially society