Advertising, incentives, and the upsell: how advertising differentially moderates customer- vs. retailer-directed price incentives' impact on consumers' preferences for premium products.

Many durable goods firms use price promotion strategies and advertising simultaneously to impact consumer preferences among vertically differentiated product offerings. In this research, we use a large secondary dataset of automotive purchases (N = 323,959) to investigate how advertising spending differentially moderates the positive impact of both customer- and retailer-directed price incentives on consumers' premium level of purchase for vertically differentiated products. We find that higher advertising spending magnifies the positive impact of customer-directed price incentives on consumers' preference for more premium purchases. In contrast, higher advertising spending attenuates the positive impact of retailer-directed price incentives on consumers' preference for more premium purchases. Our work is distinct from previous research, which has almost exclusively focused on the CPG industry and the effects of advertising and price promotions on general demand metrics-instead of consumers' preferences for premium products. Our work has important implications for practitioners and consumer welfare.

What's my age again? The influence of subjective age on consumer health-related attitudes.

We examine how shifts in subjective age influence consumer health-related attitudes. In Study 1, participants made to feel subjectively young (vs. old) exhibited more positive attitudes after viewing a health-related marketing message. Underlying this effect, subjectively young (vs. old) participants experienced higher levels of self-esteem. Study 2 tested our process by manipulating subjective physical, as opposed to mental age. Our research is the first to investigate the impact of temporary changes in subjective age on consumer attitudes towards healthy behaviors, and the first to compare the effects of mental (vs. physical) subjective age on these attitudes.

The importance of pesticide exposure duration and mode on the foraging of an agricultural pest predator.

The striped lynx spider (Oxyopes salticus), is a natural predator of crop pests and therefore frequently encounters pesticides on its substrate and its prey. While pesticide exposure may negatively impact the lifespan of spiders, sublethal effects can also alter their normal behaviors. This study examined how prey capture was affected when spiders and their prey were exposed to bifenthrin and malathion. When spiders were continually exposed to bifenthrin residues, prey capture decreased over time, but mortality was not affected. Malathion exposed spiders, however, showed increased mortality, but their ability to catch prey was unaltered. When spiders encountered pesticide dosed prey, predation was unaffected, implying that spiders are unable to detect residues on prey. These results improve the understanding of how pesticides affect natural pest control and raise questions about the functional roles that spiders play when exposed to different chemicals.

Periodontal Inflammation Primes the Systemic Innate Immune Response.

The presence of periodontal diseases (PDs) often strongly correlates with other severe chronic inflammatory conditions, including cardiovascular disease, diabetes, and arthritis. However, the mechanisms through which these diseases interact are unclear. In PD, tissue and bone destruction in the mouth is driven by elevated recruitment of polymorphonuclear neutrophils (PMNs), which are primed and recruited from the circulation to sites of inflammation. We predicted that systemic effects on PMN mobilization or priming could account for the interaction between PD and other inflammatory conditions. We tested this using a mouse model of ligature-induced PD and found elevated PMN counts specifically in bone marrow, supporting a systemic effect of periodontal tissue inflammation on PMN production. In contrast, mice with induced peritonitis had elevated PMN counts in the blood, peritoneum, and colon. These elevated counts were further significantly increased when acute peritonitis was induced after ligature-induced PD in mice, revealing a synergistic effect of multiple inflammatory events on PMN levels. Flow cytometric analysis of CD marker expression revealed enhanced priming of PMNs from mice with both PD and peritonitis compared to mice with peritonitis alone. Thus, systemic factors associated with PD produce hyperinflammatory PMN responses during a secondary infection. To analyze this systemic effect in humans, we induced gingival inflammation in volunteers and also found significantly increased activation of blood PMNs in response to ex vivo stimulation, which reverted to normal following resolution of gingivitis. Together, these results demonstrate that periodontal tissue inflammation has systemic effects that predispose toward an exacerbated innate immune response. This indicates that peripheral PMNs can respond synergistically to simultaneous and remote inflammatory triggers and therefore contribute to the interaction between PD and other inflammatory conditions. This suggests larger implications of PD beyond oral health and reveals potential new approaches for treating systemic inflammatory diseases that interact with PD.

Bilateral arthrodesis of the distal tibiofibular joint for deforming osteochondromatas.

The first case of bilateral distal tibiofibular joint fusions for osteochondromas is reported with excellent long-term outcomes.

Severe pelvic fracture with profound hypotension: a case report and treatment algorithm.

Approximately 9% of all blunt trauma patients suffer pelvic fractures. These fractures can range from insignificant and requiring almost no therapy to massive destruction of the pelvic ring with associated with multisystem injury and life-threatening hypotension which mandates the attention of the trauma surgeon, the orthopedic surgeon, the interventional radiologists and possibly other subspecialists. We present a case of a patient who presented to the emergency room in extremis from massive bleeding from a complex pelvic fracture. The patient developed abdominal compartment syndrome. The patient was emergently taken to the operating room but we were unable to control his pelvic bleeding. We propose an algorithm which might be helpful in these critically ill patients.

Ischaemia induced cell death in tumors: importance of temperature and pH.

PURPOSE: Increasing attention has focussed on the therapeutic potential of agents which can reduce tumor blood flow and induce ischaemia for long enough to result in tumor cell death. A confounding factor in this approach is the fact that the core temperature of superficial tumors reduces when the supplying blood flow is occluded and therefore protects the tumor cells from "metabolic" death. Consequently, we have tested the importance of tumor temperature on the relationship between vascular occlusion and cell death. METHODS AND MATERIALS: The murine tumor CaNT used in this study was implanted subcutaneously in the dorsum. Total vascular occlusion was achieved by physically occluding the blood supply to the tumors for periods between 1 and 20 h. The mouse temperature was controlled by placing the whole body in a thermostatically controlled incubator maintained at 35 degrees C. Tumor cell survival was assessed using an excision assay and by measuring the delay in growth of treated tumors. Measurement of tumor pH was achieved using microelectrodes. RESULTS: The core temperature of unclamped tumors was approximately 33 degrees C, but fell by about 5 degrees C during vascular occlusion at room temperature. Tumor cell survival was decreased with increasing periods of vascular occlusion at room temperature, but a greater reduction in cell survival and correspondingly increased regrowth delay was observed when the tumor temperature was prevented from cooling below preocclusion values. The extracellular pH (pHe) fell during vascular occlusion and this reduction was greater when the tumor temperature was maintained at preocclusion values. This extracellular acidosis is expected to partly explain the observation of greater tumor cell death in those tumors whose temperature does not reduce during occlusion. CONCLUSION: The temperature of superficial tumors reduces in response to vascular occlusion. This may result in an underestimation of the cytotoxicity of agents which reduce tumor blood flow as the tumor cooling protects the cells from the acidosis that accumulates within the occluded tumor.

Time and dose studies of the effect of cobra venom factor on the in vivo immune response in Galleria mellonella to Pseudomonas aeruginosa.

The induced resistance of wax moth larvae vaccinated with formolized Pseudomonas aeruginosa 18 hr prior to challenge with the live organism was significantly inhibited by 0.2 to 1.0 units of cobra venom factor (CVF) per insect given 6 hr after vaccination. Approximately 90% inhibition of the protective response was caused by 1.0 units CVF/insect. Administration of this dose 6 hr before vaccination, with the vaccine, and 6 hr before challenge had no significant effect. The CVF effect was inhibited by heating the CVF preparation at 70 degrees for 30 min.

Cane sugar factor as an inducing agent of immunity in Galleria mellonella.

The injection of cane sugar factor (CSF) into Galleria mellonella larvae results in an immune response similar to that produced by a formalized Pseudomonas aeruginosa vaccine. Vaccination with CSF is followed by: an increase in the LD50 of Pseudomonas aeruginosa; an in vivo protective response to P. aeruginosa the development of which can be inhibited by cobra venom factor (CVF); an antibacterial activity in hemolymph 24 h after the injection of CSF; the development of a transferrable immune response in hemolymph of donor larvae capable of protecting recipient larvae against a lethal challenge of Pseudomonas aeruginosa; an increase in extracellular lysozyme equal to that induced by Pseudomonas vaccine; a reduction in total hemocyte count during the period of protective immunity; and the presence in hemolymph of new basic proteins, with electrophoretic mobilities and appearance times after the CSF injection, identical to those induced by the formalized vaccine. CSF was shown to be composed primarily of glucose.

Gallysin-1, an antibacterial protein isolated from hemolymph of Galleria mellonella.

An inducible hemolysin with antibacterial properties was isolated from the hemolymph of immune Galleria mellonella larvae. The Galleria-derived lysin, named Gallysin-1, was shown to have an apparent molecular weight of 75,000 and to be relatively heat stable at 56 degrees C. Although Gallysin alone was not bactericidal it caused sufficient damage of the outer cell membranes of Pseudomonas aeruginosa RP4 and Escherichia coli K176 to release beta-lactamase from the periplasm. In the presence of either purified Galleria lysozyme or egg white lysozyme Gallysin-1 had potent antibacterial activity against gram-negative bacteria. Gallysin-1 killed osmotically shocked P. aeruginosa and E. coli that suggests that it can also attack exposed inner cell membranes of gram-negative bacteria. The identification of Gallysin-1 recognizes another distinct member of the bactericidins involved in insect immunity.

A cobra venom factor (CVF)-induced C3 convertase activity in the hemolymph of Galleria mellonella.

A cobra venom factor (CVF)-induced C3 convertase has been generated from the hemolymph of Galleria mellonella. CVF was immobilized on Sepharose 4B and treated with cell-free hemolymph obtained from either unvaccinated G. mellonella larvae or larvae immunized with formalized Pseudomonas aeruginosa. The C3-cleaving activity was detected by the ability to cleave the alpha-chain of bovine C3 in a manner analogous to the CVF-induced mammalian C3 convertase, CVF,Bb. The insect-derived C3 convertase formed at 28 degrees C but not at 37 degrees C, then once formed was active at both 28 degrees C and 37 degrees C. EDTA did not inhibit the formation and action of the insect derived C3 cleaving activity.

Reactions of hemocytes of immune and non-immune Galleria mellonella larvae to Proteus mirabilis.

Immune larval Galleria mellonella removed live Proteus mirabilis from the hemolymph less effectively than did non-immune larvae. This was attributed to a decline in total hemocyte counts, levels of plasmatocytes and granulocytes and hemocyte adhesion capacity. Immune serum possessed factors which reduced bacterial adhesion to the hemocytes. This was not due to altering bacterial surfaces but rather to irreversible suppression of hemocyte activity.

Transfer of immunity against Pseudomonas aeruginosa P11-1 in Galleria mellonella larvae.

Larvae of Galleria mellonella may be immunized against Pseudomonas aeruginosa by the transfer of whole hemolymph, cell-free hemolymph or hemocytes from insects previously immunized with the lipopolysaccharide of the homologous organisms. Whole immune hemolymph injected as early as 3 hours after vaccination confers protection which persists as long as 40 hours. Hemocytes alone confer good protection when transferred as early as 30 minutes after, and up to about 4 hours after immunization. Transferred protection does not appear to be due to excess immunogen in the hemolymph.

The hemolytic activity of Galleria mellonella hemolymph.

A hemolytic activity was identified in the hemolymph of normal and immune Galleria mellonella larvae. The hemolysin was active against sheep, human, guinea pig, and rabbit erythrocytes. Hemolysis occurred in the presence of 0.04M EDTA. Vaccination of the larvae with formalized Pseudomonas aeruginosa increased the hemolytic activity. The increase, and subsequent decline of this activity paralleled the pattern of induced in vivo antibacterial activity that is characteristic of the insect's immune response. The hemolytic activity was distinct from induced phospholipase A-like and phospholipase C-like activities that were detected in immune hemolymph and which were inhibited by EDTA. The hemolytically active material (HAM) was partially purified (apparent molecular weight range 69,000 to 75,000) and was found not to be antibacterial for P. aeruginosa. The physiological role of the HAM is as yet unknown. It is possible that it may act together with other hemolymph components to produce an immune state.

Characterization of hemolytic and cytotoxic Gallysins: a relationship with arylphorins.

Gallysin-1, an inducible effector protein in the protective response of Galleria mellonella larvae is a 75 kDa component of hemolytically active material (HAM) isolated from immune cell-free hemolymph. The sequence of the first 20 N-terminal amino acids of the antibacterial protein Gallysin-1 is identical to the predicted sequence of the first 20 amino acids of the Galleria arylphorin Lhp76 (larval hemolymph protein 76). A murine monoclonal antibody to the 20 amino acid N-terminal peptide of Gallysin-1 (GYPQYHYDVETRKLDPSLVN) provides additional evidence for a link between Gallysin-1 and Lhp76, and is used to characterize HAM further. HAM, initially characterized as a mixture of two proteins, Gallysin-1 and a 69 kDa component is now identified as a 450-500 kDa heteromultimer, designated Gallysin. In vivo levels of Gallysin rise during the effector phase of an induced immune response. The monoclonal antibody inhibits the hemolytic activity of Gallysin. In addition to a hemolytic activity for mammalian erythrocytes, Gallysin possesses a cytotoxic activity for the human tumor cell line, K562. Lipopolysaccharides (LPS) and a Pseudomonas aeruginosa vaccine induce a cytotoxic activity which reaches its maximum levels in the hemolymph early (2 hours post-vaccination) in the protective response. The partially purified cytotoxic material (Cyt-M) obtained from cell-free hemolymph collected 2 hours after vaccination has hemolytic activity and shows structural similarities to Gallysin and Lhp76. The previously established role of Gallysin-1 as an effector protein in the protective response of Galleria mellonella indicates that arylphorins may play a role in insect immune responses.

Effects of hemolymph from immune and non-immune larvae of Galleria mellonella on the ultra-structure of Pseudomonas aeruginosa.

The ultrastructure of Pseudomonas aeruginosa, a pathogen of Galleria mellonella is rapidly altered after in vitro exposure to the hemolymph of vaccinated larvae. The bacteria were treated with normal and immune hemolymph for periods of time ranging from 7 to 28 min at 28 degrees C. In contrast to the apparent non-damaging effects of normal hemolymph, the immune hemolymph caused progressive damage to the cells within 7 min. The initial attack was directed towards the cell wall. Complete degradation was observed after 14 to 28 min exposure to the immune hemolymph.

The in vitro generation of an antibacterial activity from the fat body and hemolymph of non-immunized larvae of Galleria mellonella.

A state of immunity in Galleria mellonella against the pathogen Pseudomonas aeruginosa is known to be induced by the injection of lipopolysaccharide (LPS), isolated from the homologous organism. An in vitro mixture of the LPS and whole or cell-free hemolymph from non-immunized larvae is not antibacterial. In vitro mixtures of fat body and cell-free hemolymph from non-immunized larvae, incubated at 25 degrees C for 20 hours generated a proteinaceous antibacterial activity. The generation of this activity was enhanced by the presence in the incubation mixture of LPS and/or hemocytes from non-immunized larvae. It is suggested that LPS causes the release of a hemocyte factor(s) which acts in conjunction with or directly on the fat body resulting in an enhanced production of antibacterial factors.

Non-specific antiviral activity of antisense molecules targeted to the E1 region of human papillomavirus.

Antisense phosphorothioate oligonucleotides (ODN1 0x5 OMe) directed against the E1 start region of human papillomavirus 11 (HPV11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. Administration of a mismatch control oligonucleotide (ODN9 0x5 OMe), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. However, the apparent antiviral activity of ODN1 0x5 OMe was also shown in a lethal mouse cytomegalovirus (CMV) model, in which the oligonucleotides are not expected to have antisense activity. To understand the mechanisms of action of these oligonucleotides, a mismatch oligonucleotide (ODN61 0x5 OMe) was prepared which retained the CpG motifs of ODN1 0x5 OMe. This was tested in the mouse xenograft model and shown to have moderate inhibitory activity. As a definitive experiment, a comparison was made between the efficacy of the active oligonucleotide ODN1 0x5 OMe against two papilloma viruses HPV11 and HPV40. Both these viruses cause benign genital warts, but differ by four bases in their E1 sequence that was the target for ODN1 0x5 OMe. Papillomavirus induced growth in the mouse xenograft model was inhibited by ODN1 0x5 OMe in both cases, suggesting that oligonucleotide molecules have a non-specific antiviral activity that is not directly related to their antisense sequence.

Antiandrogen action in the development of androgen insensitivity in S115 mouse mammary tumour cells.

Endocrine therapy for steroid-sensitive tumours often involves administration of steroid antagonists which are designed to bind to the steroid receptor and block steroid action. However, the clinical problem remains the temporary nature of the tumour regression. Since in vitro models suggest that steroid ablation itself can result in loss of steroid sensitivity of tumour cells, these studies aimed to investigate the influence of the antiandrogen ICI 141,307 on this progression. This antiandrogen exhibits both agonist and antagonist actions on androgen-regulated cellular and molecular parameters of S115 mouse mammary tumour cells in culture. Its ability to regulate mouse mammary tumour virus (MMTV) RNA production in these cells confirms that the antiandrogen-receptor complex can not only bind to the steroid response element (SRE) in the MMTV DNA sequences but also activate gene transcription. Despite these molecular abilities of this antiandrogen, it was still unable to maintain androgen sensitivity in the long term. It was able to delay progression to insensitivity of the various steroid-regulated parameters, although the different parameters were delayed for different lengths of time, but ultimately the antiandrogen was unable to prevent loss of any parameters. It is thus concluded that the nature of the ligand is critical for maintenance of steroid sensitivity: only androgen and not antiandrogen will maintain long-term response. Previous molecular models for loss of steroid response suggest that it could result from inactivation of SRE in the genome when no receptor complex is bound. However, loss of response occurred in these experiments even in the presence of an activated receptor complex capable of binding to the SRE. Possible molecular mechanisms and the clinical implications are discussed.

Identification of antigenic sites on staphylococcal enterotoxin B and toxoid.

The staphylococcal enterotoxins (SEs) are capable of causing both food poisoning and a toxic shock-like illness in man. In addition, SEs are known to act as superantigens, stimulating T-cells according to their T-cell receptor Vbeta type. Relatively little is known of their antigenic determinants and how these may relate to the structure and function of the toxins. As a step in the study of these relationships, the entire molecule of SEB was synthesized in duplicate as a series of octapeptides overlapping by seven residues. This series thus represented all the potential linear epitopes of eight residues or less. The reactivity of the octapeptide series with antisera raised to purified SEB and to formaldehyde-inactivated SEB has been used to locate several antigenic sites on native SEB and to identify antigenic differences in the toxoid. Three antigenic peptides identified from the antigenic profile were synthesized and characterized. These represented amino acids 21-32, 93-107 and 202-217 of SEB. None of these peptides affected SEB-induced T-cell proliferation. However, the occurrence or absence of cross-reactivity of these peptides with antibodies to native SEB corresponds to the degree of exposure and/or the rigidity of these regions within SEB.