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Food-related cues can increase the time a person spends in the dining room. Increasing the time a person spends dining can improve their food intake. Studies on the use of music and olfactory cues have produced conflicting results. This study explores whether the portion size effect (PSE), the portion served, influences a person's consumption and can explain the inconsistent results. The study focused on testing this phenomenon with residents in an aged-care home. Malnutrition is often a problem with residents in aged-care facilities. Exposing the residents to various cues (music, olfactory and infographics) over seven weeks with different portions of food served. Results showed that the cues did not significantly impact, but PSE did, casting doubts on studies that did not control for the portion served. Discussions of the academic and managerial implications are also provided. Refereed/Peer-reviewed

Intention measures are used as a proxy for future behaviour. Although there is often a gap between intentions and subsequent behaviour, little is known about why the intention-behaviour gap (IB-gap) occurs. This longitudinal study across Australia, New Zealand and China quantifies the IB-gap in the context of donating money, goods, and time to charities. The factors underpinning the IB-gap are documented (i.e., why intenders don’t act and non-intenders do), resulting in the development of a framework summarising 12 key reasons. Findings show that intenders don’t follow through due to perceived time/effort constraints or lack of resources. Non-intenders subsequently give due to heightened awareness and attitudes about a charity/cause, or an intrinsic motivation such as empathy. Our findings allow researchers and marketers to better understand and interpret intention metrics, with guidance on how to minimise barriers to action across three types of support behaviours. Refereed/Peer-reviewed

© 2020 American Chemical Society. Although cytokine therapy is an attractive strategy to build a more robust immune response in tumors, cytokines have faced clinical failures due to toxicity. In particular, interleukin-12 has shown great clinical promise but was limited in translation because of systemic toxicity. In this study, we demonstrate an enhanced ability to reduce toxicity without affecting the efficacy of IL-12 therapy. We engineer the material properties of a NP to meet the enhanced demands for optimal cytokine delivery by using the layer-by-layer (LbL) approach. Importantly, using LbL, we demonstrate cell-level trafficking of NPs to preferentially localize to the cell's outer surface and act as a drug depot, which is required for optimal payload activity on neighboring cytokine membrane receptors. LbL-NPs showed efficacy against a tumor challenge in both colorectal and ovarian tumors at doses that were not tolerated when administered carrier-free.

In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy., Chimeric antigen receptor (CAR) T cell therapies have impressive activity in the treatment of cancer but are associated with potentially fatal toxicities. In light of the approval of CAR T cell therapy for paediatric patients, a panel of experts from the Hematopoietic Stem Cell Transplantation (HSCT) Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the CAR T Cell Therapy-Associated Toxicity (CARTOX) Program at The University of Texas MD Anderson Cancer Center, and several other institutions have developed consensus guidelines for the use and management of these treatments in paediatric patients, which are presented herein.

The purpose of this study was to compare younger and older mice after chronic intraocular pressure (IOP) elevation lasting up to 4 days with respect to mitochondrial density, structure, and movement, as well as axonal integrity, in an ex vivo explant model. We studied 2 transgenic mouse strains, both on a C57BL/6J background, one expressing yellow fluorescent protein (YFP) in selected axons and one expressing cyan fluorescent protein (CFP) in all mitochondria. Mice of 4 months or 14 months of age were exposed to chronic IOP by anterior chamber microbead injection for 14 hours, 1, 3, or 4 days. The optic nerve head of globe--optic nerve explants were examined by laser scanning microscopy. Mitochondrial density, structure, and movement were quantified in the CFP explants, and axonal integrity was quantified in YFP explants. In control mice, there was a trend towards decreased mitochondrial density (# per mm2) with age when comparing younger to older, control mice, but this was not significant (1,947 ± 653 vs 1,412 ± 356; p = 0.19). Mitochondrial density decreased after IOP elevation, significantly, by 31%, in younger mice (p = 0.04) but trending towards a decrease, by 22%, in older mice (p=0.82) compared to age matched controls. Mitochondrial mean size was not altered after chronic IOP elevation for 14 hours or more (p ≥ 0.16). When assessing mitochondrial movement, in younger mice, 5% were mobile at any given time; 4% in the anterograde direction and 1% retrograde. In younger untreated tissue, only 75% of explants had moving mitochondria (mean = 15.8 moving/explant), while after glaucoma induction only 24% of explants had moving mitochondria (mean = 4.2 moving/explant; difference from control, p = 0.03). The distance mitochondria traveled in younger mice was unchanged after glaucoma exposure, but in older glaucoma explants the distance traveled was less than half of older controls (p < 0.0003). In younger mice, mitochondrial speed increased after 14 hours of elevated IOP (p = 0.006); however, in older glaucoma explants, movement was actually slower than controls (p = 0.02). In RGC-YFP explants, axonal integrity declined significantly after 4 days of IOP elevation to a similar degree in both younger and older mice. Older mice underwent greater loss of mitochondrial movement with chronic IOP elevation than younger mice, but suffered similar short-term axonal fragmentation in C57BL/6J mice. These transgenic strains, studied in explants, permit observations of alterations in intracellular structure and organelle activity in experimental glaucoma.

A well-established empirical generalization is that brand users are more likely than non-users to recall advertising for the brand they use. The pairing of a corporate and charity brand in advertising should create an expanded brand-user base, which should, in turn, lead to higher ad-memorability than either brand advertising alone. This study tests this hypothesis for consumer-packaged good sand charity brands in the United Kingdom and Australia. We find evidence that extends the generalization that ad-memorability is higher among brand users to charity supporters in non- profit contexts. We also find that when two brands are present, ad-memorability is highest among those who use the brand and support the partner charity. However, the uplift in ad-memorability among these dual-brand users is dampened by the lower ad-memorability experienced by those who use only one brand, due to a suspected information overload. The findings challenge accepted wisdom on the benefits of co-branded advertising and have implications for partner-selection for co-branded activities. Refereed/Peer-reviewed

Purpose The purpose of this study was to measure the full-field deformation response to IOP change in the peripapillary sclera (PPS) and astrocytic lamina cribrosa (ALC) of young and old mouse eyes ex vivo. Methods Thirty-eight transgenic reporter mice with green fluorescent protein-expressing astrocytes were studied at 2 to 4 months and 13 to 15 months old. The ALC and PPS of the explant eyes were imaged using laser scanning microscopy under controlled inflation from 10 to 30 mm Hg. Strains were estimated for the ALC and PPS from imaged volumes using digital volume correlation. Results ALC strains were significantly greater than zero nasal-temporally for both age groups (mean = 4.3% and 4.0%; each P ≤ 0.004) and significantly greater than zero in the inferior-superior direction for younger mice (P = 0.0004). Younger mice had larger ALC inferior-superior strains than older mice (P = 0.002). The ALC area and perimeter enlarged with inflation in both age groups, with a greater increase in younger than in older mice (all P ≤ 0.004). The ALC nasal-temporal diameter change was greater than inferior-superiorly, and younger mice had greater enlargement nasal-temporally than older. PPS maximum shear strain was greater in the older mice (P = 0.002). The axial lengths of older mice were 14% longer and the PPS was 16% thinner than younger mice (both P = 0.0003). Conclusions The behavior of the ALC in younger mice with inflation exhibited greater strains and enlargement of ALC area than older mice. Some strain measures in the PPS were greater in older mice, likely related to their longer axial length and thinner PPS.

Co-branded advertising, where advertisements feature two partnered brands from different categories, should ideally benefit both brands. We test this assertion by studying the effect of featuring a second brand in advertisements on ad and brand name memorability, and the role of category context on which brand is recalled. Our test covers online display advertisements for consumer-packaged brands paired with charity and retailer brands in three markets (USA, UK, and Australia). Independent sample comparisons across 54 brand pairs show that advertising two brands has a neutral effect on ad memorability and negative effect on brand memorability. Furthermore, the advertisement’s category context determines which of the brands is recalled. Our findings support a competitive interference theory of dual-brand processing, whereby the two brands compete for attention resources. The results have implications for the return on investment from advertising expenditure, which will vary substantively depending on whether the costs of advertising are shared or borne by one brand in the pair.

The Negative Binomial Distribution (NBD) is a model that describes consumer purchase frequency over time. This paper tests the applicability of this model to a novel context: physical activity behaviours (using data obtained from Australia, the United States, and Singapore). The fit of the NBD to the data demonstrates that physical activity behaviour is consistent with other consumer behaviour patterns. Within a one-week period, the majority of people are either non- or light-engagers of the different intensities of leisure-time physical activity. Yet, people are not 'active' or 'inactive', rather, degree of engagement varies. Infrequency of reported levels and variety of physical activities might be due to health promotion having a strong focus on rational persuasion and less focus on mass communication that builds mental availability. Our contribution broadens the applicability of the NBD showing it can be helpful for those seeking to promote health behaviours, not just purchases. Refereed/Peer-reviewed

At the end of the last century, Sharp and Wright (1999) documented the emergence of a school of marketing enquiry labelled as the Empirical Generalisationists. With this special edition on Empirically-Based Marketing Knowledge, we take the opportunity to update that original article, giving an overview on the health of the Empirical Generalisations research tradition. We put forward a call to action for more researchers to take up the challenge to develop scientific laws in marketing, and promote a culture of evidence-based theory and managerial decision making.

We developed an explant model of the mouse eye and optic nerve that facilitates the study of retinal ganglion cell axons and mitochondria in the living optic nerve head (ONH) in an ex vivo environment. Two transgenic mouse strains were used, one expressing yellow fluorescent protein in selected axons and a second strain expressing cyan fluorescent protein in all mitochondria. We viewed an explanted mouse eye and optic nerve by laser scanning microscopy at and behind the ONH, the site of glaucoma injury. Explants from previously untreated mice were studied with the intraocular pressure (IOP) set artificially at normal or elevated levels for several hours. Explants were also studied from eyes that had undergone chronic IOP elevation from 14 hours to 6 weeks prior to ex vivo study. Image analysis in static images and video of individual mitochondria or axonal structure determined effects of acute and chronic IOP elevation. At normal IOP, fluorescent axonal structure was stable for up to 3 hours under ex vivo conditions. After chronic IOP elevation, axonal integrity index values indicated fragmentation of axon structure in the ONH. In mice with fluorescent mitochondria, the normal density decreased with distance behind the ONH by 45% (p=0.002, t-test). Density increased with prior chronic IOP elevation to 21,300 ± 4,176 mitochondria/mm2 compared to control 16,110 ± 3159 mitochondria/mm2 (p=0.025, t-test), but did not increase significantly after 4 hours, acute IOP elevation (1.5% decrease in density, p=0.83, t-test). Mean normal mitochondrial length of 2.3 ± 1.4 μm became 13% smaller after 4 hours of IOP elevation ex vivo compared to baseline (p=0.015, t-test, N-10). Normal mitochondrial speed of movement was significantly slower in the anterograde direction (towards the brain) than retrograde, but there were more mitochondria in motion and traveling longer lengths in anterograde direction. The percent of mitochondria in motion decreased by >50% with acute IOP increase to 30 mm Hg after 60 minutes. A new ocular explant model implemented with eyes from transgenic mice with fluorescent cellular components provided real time measurement of the early events in experimental glaucoma and quantitative outcomes for neuroprotection therapy experiments.

Attention has become an area of major interest in marketing research as a dependent or moderating variable. In this article, we argue for respondent attention as a pivotal part of any consumer psychology research protocol and highlight the risks of not incorporating realistic attention components into research design. We propose four areas where this approach can help the external validity of consumer psychology research. Our recommendations include accounting for variability in the baseline attention levels; smart use of distractions; allowing for variability in attention over the task and avoiding attention leading/assumptive questions. Refereed/Peer-reviewed

Retailers often feature manufacturer brands in their advertising with the aim to drive sales for those brands and, at the same time, increase in-store traffic. The adoption of such co-operative advertising strategies should reach an expanded audience base comprising of store and brand buyers. Based on empirical evidence in non-retail settings, these buyers are more likely to remember the advertising than non-buyers. This usage-bias effect implies that co-operative advertisements achieve greater cut through than would be the case if either brand advertised alone. Our paper tests this hypothesis in the context of retailer advertisements that feature manufacturer brands in the US, UK and Australia. Our results confirm that a retail brand's shoppers are more likely to recall its advertisements than non-shoppers, extending the usage-bias generalisation to a retailing context. However, while co-operative advertising does expand the buyer-base reach, any uplift in ad-memorability is negated by a reduced ability for buyers of only one of the two brands to recall the advertisement. Information overload on cognitive processing is a possible explanation for this finding, and has implications for extracting value from any investment in co-operative advertising. Refereed/Peer-reviewed

Cathy Nguyen, aesh, s’entretient avec un membre du comite de redaction au sujet de son travail. Devoilant la complexite, les limites et les bonheurs de cette fonction pilier des dispositifs inclusifs, ses propos nous permettent de mieux en comprendre les ressorts.

The article Are two brands better than one? Investigating the effects of co-branding in advertising on audience memory, written by Cathy Nguyen, Jenni Romaniuk, Margaret Faulkner and Justin Cohen, was originally published electronically on the publisher’s internet portal (currently SpringerLink).

The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model.CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure–strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice.

The purpose of this research was to study the effects of age and genetic alterations in key connective tissue proteins on susceptibility to experimental glaucoma in mice. We used mice haploinsufficient in the elastin gene (EH) and mice without both alleles of the fibromodulin gene (FM KO) and their wild type (WT) littermates of B6 and CD1 strains, respectively. FM KO mice were tested at two ages: 2 months and 12 months. Intraocular pressure (IOP) was measured by Tonolab tonometer, axial lengths and widths measured by digital caliper post-enucleation, and chronic glaucoma damage was measured using a bead injection model and optic nerve axon counts. IOP in EH mice was not significantly different from WT, but FM KO were slightly lower than their controls (p = 0.04). Loss of retinal ganglion cell (RGC) axons was somewhat, but not significantly greater in young EH and younger or older FM KO strains than in age-matched controls (p = 0.48, 0.34, 0.20, respectively, multivariable regression adjusting for IOP exposure). Older CD1 mice lost significantly more RGC axons than younger CD1 (p = 0.01, multivariable regression). The CD1 mouse strain showed age-dependence of experimental glaucoma damage to RGC in the opposite, and more expected, direction than in B6 mice in which older mice are more resistant to damage. Genetic alteration in two genes that are constituents of sclera, fibromodulin and elastin do not significantly affect RGC loss.

This study builds on the research of East et al. (2008) into the relative impact of Positive and Negative Word of Mouth (PWOM, NWOM). It examines two low involvement categories with different consumer transaction patterns: TV programs and films. The results reveal that when prior viewing probabilities have equivalent room-to-change, PWOM and NWOM have the same level of impact for films, but PWOM is more influential than NWOM for TV programs. This is an important boundary condition for the work of East et al. (2008) and suggests that the value of NWOM should be discounted in TV programs, irrespective of the prior propensity to view. Consistent with East et al. (2008), we find that PWOM is more influential on those with lower viewing probabilities. Our findings provide guidance as to which type of viewers should be targeted with WOM campaigns to have the greatest effect on audience growth. Refereed/Peer-reviewed

The purpose of this randomized noninferiority trial was to compare video teleconferencing (VTC) versus in-person (IP) delivery of an 8-week acceptance and commitment therapy (ACT) intervention among veterans with chronic pain (N = 128) at post-treatment and at 6-month follow-up. The primary outcome was the pain interference subscale of the Brief Pain Inventory. Secondary outcomes included measures of pain severity, mental and physical health-related quality of life, pain acceptance, activity level, depression, pain-related anxiety, and sleep quality. In intent to treat analyses using mixed linear effects modeling, both groups exhibited significant improvements on primary and secondary outcomes, with the exception of sleep quality. Further, improvements in activity level at 6-month follow-up were significantly greater in the IP group. The noninferiority hypothesis was supported for the primary outcome and several secondary outcomes. Treatment satisfaction was similar between groups; however, significantly more participants withdrew during treatment in the VTC group compared with the IP group, which was moderated by activity level at baseline. These findings generally suggest that ACT delivered via VTC can be as effective and acceptable as IP delivery for chronic pain. Future studies should examine the optimal delivery of ACT for patients with chronic pain who report low levels of activity. This trial was registered at ClinicalTrials.gov ( NCT01055639 ). Perspective This study suggests that ACT for chronic pain can be implemented via VTC with reductions in pain interference comparable with IP delivery. This article contains potentially important information for clinicians using telehealth technology to deliver psychosocial interventions to individuals with chronic pain.

Background and purpose: Protease-activated receptor-4 (PAR4), the most recently discovered member of the PARs family, is activated by thrombin, trypsin and cathepsin G, but can also be selectively activated by small synthetic peptides (PAR4-activating peptide, PAR4-AP). PAR4 is considered a potent mediator of platelet activation and inflammation. As both PAR1 and PAR2 have been implicated in the modulation of nociceptive mechanisms, we investigated the expression of PAR4 in sensory neurons and the effects of its selective activation on nociception. Experimental approach and key results: We demonstrated the expression of PAR4 in sensory neurons isolated from rat dorsal root ganglia by reverse transcription-polymerase chain reaction and immunofluorescence. We found that PAR4 colocalized with calcitonin gene-related peptide and substance P. We also showed that a selective PAR4-AP was able to inhibit calcium mobilization evoked by KCl and capsaicin in rat sensory neurons. Moreover, the intraplantar injection of a PAR4-AP significantly increased nociceptive threshold in response to thermal and mechanical noxious stimuli, while a PAR4 inactive control peptide had no effect. The anti-nociceptive effects of the PAR4-AP were dose-dependent and occurred at doses below the threshold needed to cause inflammation. Finally, co-injection of the PAR4-AP with carrageenan significantly reduced the carrageenan-induced inflammatory hyperalgesia and allodynia, but had no effect on inflammatory parameters such as oedema and granulocyte infiltration. Conclusions and implications: Taken together, these results identified PAR4 as a novel potential endogenous analgesic factor, which can modulate nociceptive responses in normal and inflammatory conditions. British Journal of Pharmacology (2007) 150, 176–185. doi:10.1038/sj.bjp.0706975

Purpose To determine if oral losartan treatment decreases the retinal ganglion cell (RGC) death caused by experimental intraocular pressure (IOP) elevation in mice. Methods We produced IOP increase in CD1 mice and performed unilateral optic nerve crush. Mice received oral losartan, spironolactone, enalapril, or no drug to test effects of inhibiting angiotensin receptors. IOP was monitored by Tonolab, and blood pressure was monitored by tail cuff device. RGC loss was measured in masked axon counts and RGC bodies by β-tubulin labeling. Scleral changes that could modulate RGC injury were measured including axial length, scleral thickness, and retinal layer thicknesses, pressure-strain behavior in inflation testing, and study of angiotensin receptors and pathways by reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Results Losartan treatment prevented significant RGC loss (median loss = 2.5%, p = 0.13), while median loss with water, spironolactone, and enalapril treatments were 26%, 28% and 43%; p < 0.0001). The lower RGC loss with losartan was significantly less than the loss with spironolactone or enalapril (regression model p = 0.001; drug treatment group term p = 0.01). Both losartan and enalapril significantly lowered blood pressure (p< 0.001), but losartan was protective, while enalapril led to worse than water-treated RGC loss. RGC loss after crush injury was unaffected by losartan treatment (difference from control p = 0.9). Survival of RGC in cell culture was not prolonged by sartan treatment. Axonal transport blockade after 3 day IOP elevations was less in losartan-treated than in control glaucoma eyes (p = 0.007). Losartan inhibited effects of glaucoma, including reduction in extracellular signal-related kinase activity and modification of glaucoma-related changes in scleral thickness and creep under controlled IOP. Conclusions The neuroprotective effect of losartan in mouse glaucoma is associated with adaptive changes in the sclera expressed at the optic nerve head.

International audience; Spermatozoa contain a complex population of RNAs including messenger RNAs (mRNAs) and small RNAs such as microRNAs (miRNA). It has been reported that these RNAs can be used to understand the mechanisms by which toxicological exposure affects spermatogenesis. The aim of our study was to compare mRNA and miRNA profiles in spermatozoa from eight smokers and eight non-smokers, and search for potential relationships between mRNA and miRNA variation. All men were selected based on their answers to a standard toxic exposure questionnaire, and sperm parameters. Using mRNA and miRNA microarrays, we showed that mRNAs from 15 genes were differentially represented between smokers and non-smokers (p \textless 0.01): five had higher levels and 10 lower levels in the smokers. For the microRNAs, 23 were differentially represented: 16 were higher and seven lower in the smokers (0.004 \textless= p \textless 0.01). Quantitative RT-PCR confirmed the lower levels in smokers compared to non-smokers for hsa-miR-296-5p, hsa-miR-3940, and hsa-miR-520d-3p. Moreover, we observed an inverse relationship between the levels of microRNAs and six potential target mRNAs (B3GAT3, HNRNPL, OASL, ODZ3, CNGB1, and PKD2). Our results indicate that alterations in the level of a small number of microRNAs in response to smoking may contribute to changes in mRNA expression in smokers. We conclude that large-scale analysis of spermatozoa RNAs can be used to help understand the mechanisms by which human spermatogenesis responds to toxic substances including those in tobacco smoke.

Celebrities are one of the most commonly used elements in advertising, as both design elements to signal the brand and as creative devices to attract attention and increase the consumers’ positive attitude to the advertisement. This raises two issues. The first is that despite the cost, as celebrities can be very expensive, prior literature has provided mixed results regarding celebrity contribution to effective advertising. The second is the possibility of conflicting objectives, in that a celebrity that is a powerful enough creative device to lift the cut through of the advertising may distract rather than build attention to the brand. Therefore, an advertisement gains on one dimension of advertising effectiveness but loses on another. This multi-country study examines the strengths and weaknesses of celebrities as design elements in advertising, using advertisement recall, like ability and correct branding as advertising effectiveness measures. This research shows that celebrities cannot be used as silver bullets to guarantee effective advertising. We find no support that celebrity advertisements systematically outperform non-celebrity advertisements on any of the three advertising effectiveness measures. Category-level analysis reveals that advertisements with celebrities both outperform and under perform advertisements without celebrities. Further analysis with a classification of celebrity professions shows the superiority of athlete celebrities against non-celebrity advertisements in advertisement like ability. This suggests that there are extraneous factors which impact on advertising effectiveness when celebrities are involved. Our testing of some possible extraneous factors did not reveal anything significant. Refereed/Peer-reviewed

Parameterized shortwave and longwave algorithms developed at the Langley Research Center have been used to derive surface radiative fluxes in the processing of the Clouds and the Earth's Radiant Energy System (CERES) data obtained from flight aboard the Tropical Rainfall Measuring Mission (TRMM) satellite. Retrieved fluxes were validated on an instantaneous–footprint basis using coincident surface measurements obtained from the Atmospheric Radiation Measurement (ARM) program's Southern Great Plains (SGP) central facility, the ARM/SGP network of extended facilities, and a number of surface sites of the Baseline Surface Radiation Network (BSRN) and the Climate Monitoring and Diagnostics Laboratory (CMDL). Validation was carried out separately for clear-sky and all-sky conditions. For the shortwave, systematic errors varied from −12 to 10 W m−2 for clear skies and from −5 to 35 W m−2 for all-sky conditions. Random errors varied from 20 to 40 W m−2 for clear skies but were much larger (45–85 W m−2) f...

Purpose To determine if retinal ganglion cell (RGC) axon loss in experimental mouse glaucoma is uniform in the optic nerve. Methods Experimental glaucoma was induced for 6 weeks with a microbead injection model in CD1 (n = 78) and C57BL/6 (B6, n = 68) mice. From epoxy-embedded sections of optic nerve 1 to 2 mm posterior to the globe, total nerve area and regional axon density (axons/1600 μm2) were measured in superior, inferior, nasal, and temporal zones. Results Control eyes of CD1 mice have higher axon density and more total RGCs than control B6 mice eyes. There were no significant differences in control regional axon density in all mice or by strain (all P > 0.2, mixed model). Exposure to elevated IOP caused loss of RGC in both strains. In CD1 mice, axon density declined without significant loss of nerve area, while B6 mice had less density loss, but greater decrease in nerve area. Axon density loss in glaucoma eyes was not significantly greater in any region in either mouse strain (both P > 0.2, mixed model). In moderately damaged CD1 glaucoma eyes, and CD1 eyes with the greatest IOP elevation exposure, density loss differed by region (P = 0.05, P = 0.03, mixed model) with the greatest loss in the temporal and superior regions, while in severely injured B6 nerves superior loss was greater than inferior loss (P = 0.01, mixed model, Bonferroni corrected). Conclusions There was selectively greater loss of superior and temporal optic nerve axons of RGCs in mouse glaucoma at certain stages of damage. Differences in nerve area change suggest non-RGC responses differ between mouse strains.

Purpose To develop an ex vivo explant system using multiphoton microscopy and digital volume correlation to measure the full-field deformation response to intraocular pressure (IOP) change in the peripapillary sclera (PPS) and in the optic nerve head (ONH) astrocytic structure. Methods Green fluorescent protein (GFP)-glutamate transporter-GLT1 (GLT1/GFP) mouse eyes were explanted and imaged with a laser-scanning microscope under controlled inflation. Images were analyzed for regional strains and changes in astrocytic lamina and PPS shape. Astrocyte volume fraction in seven control GLT1/GFP mice was measured. The level of fluorescence of GFP fluorescent astrocytes was compared with glial fibrillary acidic protein (GFAP) labeled astrocytes using immunohistochemistry. Results The ONH astrocytic structure remained stable during 3 hours in explants. Control strain-globally, in the central one-half or two-thirds of the astrocytic lamina-was significantly greater in the nasal-temporal direction than in the inferior-superior or anterior-posterior directions (each P≤ 0.03, mixed models). The PPS opening (perimeter) in normal eye explants also became wider nasal-temporally than superior-inferiorly during inflation from 10 to 30 mm Hg (P = 0.0005). After 1 to 3 days of chronic IOP elevation, PPS area was larger than in control eyes (P = 0.035), perimeter elongation was 37% less than controls, and global nasal-temporal strain was significantly less than controls (P = 0.007). Astrocyte orientation was altered by chronic IOP elevation, with processes redirected toward the longitudinal axis of the optic nerve. Conclusions The explant inflation test measures the strain response of the mouse ONH to applied IOP. Initial studies indicate regional differences in response to both acute and chronic IOP elevation within the ONH region.

While word of mouth (WOM) is regarded as a key ingredient in product success, little is known about the content of WOM given. Using an online text-mining approach, we investigated the key themes within electronic WOM (eWOM) in two entertainment categories, television programs and movies. We identified seven key themes within eWOM conversations. These were (in order of prevalence): Product/Service Characteristic (26% of comments); Personal Opinion (17%); Distribution Characteristic (15%); Categorisation Comparison (14%); Description of Purchase/Consumption Activity (10%); Advertising/Promotion (9%) and In-Market Performance (4%). There were differences across categories, largely explainable by differences in the purchase/consumption process of movies versus television programs. However, there were only minor differences for new versus returning products. Our findings highlight the value of advertising during the initial stages of a product's launch to enable consumers to form opinions early on. Furthermore, marketing activities should provide information about how people can purchase/consume the product/service, as such details are often sought and passed on via eWOM. Given that eWOM often entails a comparison of a given product against another, providing signals on appropriate comparative offerings may help marketers control the context for consumers' understanding of the new product. Refereed/Peer-reviewed

The formulation to account for effects of propeller angle of attack on acoustic radiation by propellers is presented. A propeller operating at an angle of attack presents a nonuniform ine ow situation that is known to have a pronounced ine uence on noise. Noise predictions, based on this new formulation, are compared with measured wind-tunnel data. Predictions for observers e xed in the propeller plane are also included to assess the ine uence of shaft angle of attack. Nomenclature c0 = ambient speed of sound f = function dee ning blade surface l = local force per unit area of blade acting on e uid lr = component of loading vector in direction of radiation vector, liri M = source Mach number Mr = component of source Mach vector in direction of

PURPOSE To study anatomical changes and mechanical behavior of the sclera in mice with experimental glaucoma by comparing CD1 to B6 mice. METHODS Chronic experimental glaucoma for 6 weeks was produced in 2- to 4-month-old CD1 (43 eyes) and B6 mice (42 eyes) using polystyrene bead injection into the anterior chamber with 126 control CD1 and 128 control B6 eyes. Intraocular pressure (IOP) measurements were made with the TonoLab at baseline and after bead injection. Axial length and scleral thickness were measured after sacrifice in the CD1 and B6 animals and compared to length data from 78 eyes of DBA/2J mice. Inflation testing of posterior sclera was conducted, and circumferential and meridional strain components were determined from the displacement response. RESULTS Experimental glaucoma led to increases in axial length and width by comparison to fellow eyes (6% in CD1 and 10% in B6; all P < 0.03). While the peripapillary sclera became thinner in both mouse types with glaucoma, the remainder of the sclera uniformly thinned in CD1, but thickened in B6. Peripapillary sclera in CD1 controls had significantly greater temporal meridional strain than B6 and had differences in the ratios of meridional to effective circumferential strain from B6 mice. In both CD1 and B6 mice, exposure to chronic IOP elevation resulted in stiffer pressure-strain responses for both the effective circumferential and meridional strains (multivariable regression model, P = 0.01-0.03). CONCLUSIONS Longer eyes, greater scleral strain in some directions at baseline, and generalized scleral thinning after glaucoma were characteristic of CD1 mice that have greater tendency to retinal ganglion cell damage than B6 mice. Increased scleral stiffness after glaucoma exposure in mice mimics findings in monkey and human glaucoma eyes.

Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic example for fine-tuning of the transition between planktonic and community lifestyles through two-component systems (TCS). Here we decipher the regulon of the P. aeruginosa response regulator PprB of the TCS PprAB. We identified genes under the control of this TCS and once this pathway is activated, analyzed and dissected at the molecular level the PprB-dependent phenotypes in various models. The TCS PprAB triggers a hyper-biofilm phenotype with a unique adhesive signature made of BapA adhesin, a Type 1 secretion system (T1SS) substrate, CupE CU fimbriae, Flp Type IVb pili and eDNA without EPS involvement. This unique signature is associated with drug hyper-susceptibility, decreased virulence in acutely infected flies and cytotoxicity toward various cell types linked to decreased Type III secretion (T3SS). Moreover, once the PprB pathway is activated, decreased virulence in orally infected flies associated with enhanced biofilm formation and dissemination defect from the intestinal lumen toward the hemolymph compartment is reported. PprB may thus represent a key bacterial adaptation checkpoint of multicellular and aggregative behavior triggering the production of a unique matrix associated with peculiar antibiotic susceptibility and attenuated virulence, a particular interesting breach for therapeutic intervention to consider in view of possible eradication of P. aeruginosa biofilm-associated infections., Author Summary We unraveled that once the two-component system PprAB regulatory pathway is activated, Pseudomonas aeruginosa displays a unique hyper-biofilm phenotype due to a molecular signature combining a T1SS high molecular weight substrate, BapA, fimbriae of the chaperone-usher pathway, Type IVb pili and eDNA. Originally, this particular hyper-biofilm that is not strictly dependent on Psl or Pel exopolysaccharide (EPS) synthesis displays increased drug susceptibility, in contrary to previously reported biofilm lifestyle associated with increased resistance to antibiotics. PprB-dependent hyper-biofilm was also observed on intestinal mucosa of orally infected Drosophila flies in which it also displays a reduced capacity to cross the epithelial barrier from the intestinal lumen toward the hemolymph that consequently resulted in a reduced capacity to kill flies. Furthermore, constitutive activation of this PprB regulatory pathway triggers a reduced secretion of T3SS effectors which may account for the decreased virulence observed in epithelial and macrophage lineages and in acute Drosophila infections induced by septic injury. We appended in this study pieces of regulatory and molecular data that highlight the possibility to combat infections due to P. aeruginosa-biofilm with particular matrix.

Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model.At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)-dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC(50)) for COX isoenzymes.Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E(2) and FITC-dextran elevation (P 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E(2) elevation (P 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC(50) for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC(50) for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels.Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC-dextran leakage. The difference in inflammation suppression may be due to differences in tissue concentrations and/or greater COX-1 suppression by ketorolac 0.45%.

This paper shows that respondents are better at predicting when they won’t give a recommendation than when they will. The main reason for inaccuracy was an over-reliance on past circumstances (past receiving or giving of recommendations) in making future predictions of their own behaviour. Therefore, self-report probabilities are best used as measures of the potential or desire to give a recommendation, rather than predictions of future behaviour. The translation of this potential to behaviour will depend largely on the external environment, which is outside the respondent’s control. To improve the accuracy of aggregatelevel predictions of how many people will give recommendations, we suggest reducing the number of those with a high self-reported probability to around 30% of survey estimates. Refereed/Peer-reviewed

Identification of markers associated with melanoma progression is crucial to identify new prognostic and/or therapeutic targets.By using DNA microarrays, two human melanoma cell lines, M4Be and Tw12, derived from the same tumor, but with different metastatic potential, were profiled. Western blot of cell lines, immunohistochemistry on melanoma biopsies and in silico analyses validated and extended our results.Thirty-six clones were differentially-expressed between the two cell lines, representing 33 named genes and 2 expressed sequence tags. The most up-regulated gene in the strongly metastatic clone Tw12 was CD10. Protein analysis with anti-CD1O antibody confirmed this finding in cell lines and clinical samples with expression being more frequent in metastatic compared to primary tumors. Many up-regulated genes were involved in angiogenesis, invasion, growth and apoptosis. Down-regulated genes included tumor suppressor genes and those were involved in differentiation.We identified several genes the expression of which is associated with metastatic progression in human melanoma cells. Although further analyses are warranted to clarify their exact role in tumor progression, they might lead to new prognostic markers and/or molecular therapeutic targets in metastatic melanoma.

Proteinase-activated receptor-2 (PAR2) activation induces colonic inflammation by an unknown mechanism. We hypothesized that PAR2 agonists administered intracolonically in mice induce inflammation via a neurogenic mechanism. Pretreatment of mice with neurokinin-1 and calcitonin-gene-related peptide (CGRP) receptor antagonists or with capsaicin showed attenuated PAR2-agonist-induced colitis. Immunohistochemistry demonstrated a differential expression of a marker for the type-1 CGRP receptor during the time course of PAR2-agonist-induced colitis, further suggesting a role for CGRP. We conclude that PAR2-agonist-induced intestinal inflammation involves the release of neuropeptides, which by acting on their receptors cause inflammation. These results implicate PAR2 as an important mediator of intestinal neurogenic inflammation.Key words: trypsin, proteinase-activated receptor-2, colitis, neurogenic inflammation, substance P, neurokinin-1 receptors, calcitonin-gene-related peptide.

New Zeland Black (NZB) mice develop an autoimmune disease involving an abnormal B cell response to peripheral self Ags. This disease is associated with defects in other cell types and thymic stromal organization. We present evidence that NZB cells of various lineages, including thymocytes, fibroblasts, and dendritic precursor cells, show impaired proliferation and enhanced cell death in culture upon stimulation compared with non-autoimmune-prone mice such as C57BL/6. This phenotype explains the reduced efficiency of maturation of bone marrow-derived dendritic cells and the loss of TNF- or IL-1-dependent thymocyte costimulation. Upon TNF-induced activation of NZB thymocytes, nuclear translocation and DNA binding of RelA- and RelB-dependent NF-κB heterodimers are significantly reduced. This phenotype has a transcriptional signature, since the NZB, but not the nonobese diabetic, thymic transcriptome shows striking similarities with that of RelB-deficient thymuses. This partial NF-κB deficiency detected upon activation by proinflammatory cytokines could explain the disorganization of thymic microenvironments in NZB mice. These combined effects might reduce the efficiency of central tolerance and expose apoptotic debris generated during inflammatory processes to self recognition.

The National Aeronautics and Space Administration (NASA) Aircraft Noise Prediction Program (ANOPP) Propeller Analysis System (PAS) is a set of computational modules for predicting the aerodynamics, performance, and noise of propellers. The ANOPP PAS has the capability to predict noise levels for propeller aircraft certification and produce parametric scaling laws for the adjustment of measured data to reference conditions. A technical overview of the prediction techniques incorporated into the system is presented. The prediction system has been applied to predict the noise signature of a variety of propeller configurations including the effects of propeller angle of attack. A summary of these validation studies is discussed with emphasis being placed on the wind tunnel and flight test programs sponsored by the Federal Aviation Administration (FAA) for the Piper Cherokee Lance aircraft. A number of modifications and improvements have been made to the system and both DEC VAX and IBM-PC versions of the system have been added to the original CDC NOS version.