Serum proteins on nanoparticles: early stages of the "protein corona".

Nanoparticles in biological systems such as the bloodstream are exposed to a complex solution of biomolecules. A "corona" monolayer of proteins has historically been thought to form on nanoparticles upon introduction into such environments. To examine the first steps of protein binding, Fluorescence Correlation/Cross Correlation Spectroscopy and Fluorescence Resonance Energy Transfer were used to directly analyze four different nanoparticle systems. CdSe/ZnS core/shell quantum dots, 100 nm diameter polystyrene fluospheres, 200 nm diameter polystyrene fluospheres, and 200 nm diameter PEG-grafted DOTAP liposomes were studied with respect to serum protein binding, using bovine serum albumin as a model. Surface heterogeneity is found to be a key factor in protein binding to these nanoparticles, and as such we present a novel conceptualization of the early hard corona as low-ratio, non-uniform binding rather than a uniform monolayer.

An external telemetry system for recording resting heart rate variability and heart rate in free-ranging large wild mammals.

Measures of heart rate variability (and heart rate more generally) are providing powerful insights into the physiological drivers of behaviour. Resting heart rate variability (HRV) can be used as an indicator of individual differences in temperament and reactivity to physical and psychological stress. There is increasing interest in deriving such measures from free ranging wild animals, where individuals are exposed to the natural and anthropogenic stressors of life. We describe a robust, externally mounted heart rate monitor for use in wild mammals, deployed here on wild breeding adult female grey seals (Halichoerus grypus), that delivers millisecond precise measures of inter beat intervals (IBIs), allowing computation of resting HRV parameters. Based on Firstbeat™ heart rate belts, our system allows for remote, continuous recording of IBI data from over 30 individuals simultaneously at ranges of up to 200m. We assessed the accuracy of the IBI data provided by the Firstbeat™ system using concurrent IBI data derived from in-field electrocardiogram (ECG) recordings. Bland-Altmann analyses demonstrated high correspondence between the two sets of IBI data, with a mean difference of 0.87±0.16ms. We used generalized additive mixed-effects models to examine the impact of the default Firstbeat™ software artefact correction procedure upon the generation of anomalous data (flats and stairs). Artefact correction and individual activity were major causes of flats and stairs. We used simulations and models to assess the impact of these errors on estimates of resting HRV and to inform criteria for subsampling relatively error free IBI traces. These analyses allowed us to establish stringent filtering procedures to remove traces with excessive numbers of artefacts, including flats and stairs. Even with strict criteria for removing potentially erroneous data, the abundance of data yielded by the Firstbeat™ system provides the potential to extract robust estimates of resting HRV. We discuss the advantages and limitations of our system for applications beyond the study system described here.

Reactive stress-coping styles show more variable reproductive expenditure and fitness outcomes.

Stress-coping styles dictate how individuals react to stimuli and can be measured by the integrative physiological parameter of resting heart-rate variability (HRV); low resting HRV indicating proactive coping styles, while high resting HRV typifies reactive individuals. Over 5 successive breeding seasons we measured resting HRV of 57 lactating grey seals. Mothers showed consistent individual differences in resting HRV across years. We asked whether proactive and reactive mothers differed in their patterns of maternal expenditure and short-term fitness outcomes within seasons, using maternal daily mass loss rate to indicate expenditure, and pup daily mass gain to indicate within season fitness outcomes. We found no difference in average rates of maternal daily mass loss or pup daily mass gain between proactive and reactive mothers. However, reactive mothers deviated more from the sample mean for maternal daily mass and pup daily mass gain than proactive mothers. Thus, while proactive mothers exhibit average expenditure strategies with average outcomes, expenditure varies much more among reactive mothers with more variable outcomes. Overall, however, mean fitness was equal across coping styles, providing a mechanism for maintaining coping style diversity within populations. Variability in reactive mothers' expenditures and success is likely a product of their attempts to match phenotype to prevailing environmental conditions, achieved with varying degrees of success.

Space use of Pacific harbor seals (Phoca vitulina richardii) from two haulout locations along the Oregon coast.

BACKGROUND: There are approximately 10,000-12,000 Pacific harbor seals (Phoca vitulina richardii) inhabiting the Oregon coast, and unlike other species of pinnipeds in this region, are reliably present year-round. Despite this, and drastic rebounds in population since the enactment of the Marine Mammal Protection Act, limited data is available for the present period regarding their space use at sea, and within estuarine, riverine, or bay areas within the state. OBJECTIVE: To examine site-based differences in space use for 24 adult Pacific harbor seals captured and outfitted with satellite transmitters at two predominant haulout sites on the Oregon Coast, USA. DESIGN: We captured 24 adult harbor seals from two haulout sites on the Central Oregon coast between September 2014-16 and fitted them with external Wildlife Computers SPOT5 satellite transmitters to track movement. Using state-space modeled locations derived from satellite telemetry data, we evaluated spatial behavior of these animals using a correlated random walk model via R package crawl. Kernel density estimation was subsequently used to calculate home range and core area for each animal. Percent use of open ocean habitat versus use of estuaries, rivers and bays was quantified, as was an initial examination of presence within five newly-established marine reserves in Oregon. Examination of haulout site-related differences in spatial behavior were examined for seals captured in Netarts and Alsea Bays, Oregon and haul out behavior related to time of day, season, and tidal level was also investigated. RESULTS: The average individual home range for seals was 364.47 ± 382.87 km2 with seals captured in Alsea bay demonstrating a significantly higher home range area than those captured in Netarts Bay. Alsea bay seals also tended to range farther from shore than Netarts Bay animals. The average calculated core area for seals encompassed on average 29.41 ± 29.23 km2 per animal, however the home range of one animal was so small, core area could not be calculated. Use of marine reserves was limited for animals in this study, representing less than 2% of locations with a majority occurring in Cape Perpetua Marine Reserve and North Marine Protected Area. Seals were more likely to haul out during low tides and periods of low light (dusk, night and dawn), and hauling out behavior increased in winter months. SIGNIFICANCE: These findings demonstrate the first major documentation of space use of harbor seals in the state for nearly three decades, and lends itself to future comparison and formation of mechanistically-based hypotheses for behavior of a common marine mammal in the highly productive northern California Current System.

Characterizing estrus by trans-abdominal ultrasounds, fecal estrone-3-glucuronide, and vaginal cytology in the Steller sea lion (Eumetopias jubatus).

The ability to monitor the estrus cycle in wild and captive marine species is important for identifying reproductive failures, ensuring a successful breeding program, and monitoring animal welfare. Minimally invasive sampling methods to monitor estrus in captive populations have been developed, but results suggest these tools can be species-specific in their precision and accuracy. Therefore, the minimally invasive sampling methods of trans-abdominal ultrasounds, a fecal steroid analysis (estrone-3-glucuronide, E1G), and vaginal cytology, were evaluated for their efficacy to characterize and monitor estrus in a captive breeding population of Steller sea lions (Eumetopias jubatus). Three adult females were sampled over five breeding seasons, resulting in six estrus profiles characterized by trans-abdominal ultrasounds, five by fecal E1G, and four by vaginal cytology. Animals were trained to allow trans-abdominal ultrasounds, fecal samples, and vaginal swabs to be collected approximately daily. Of the 76 trans-abdominal ultrasound sessions attempted, 8 successfully visualized both ovaries. From these scans, the chronology of ovarian changes during proestrus and estrus was estimated. The time from the detection of developing follicles to the identification of a dominate follicle occurred in 2-5 days and a corpus hemorrhagicum formed approximately 4 days later. However, because visualization of the ovaries was prevented by the gastrointestinal system in 88% of scans, this tool was overall unreliable for monitoring changes associated with estrus. To detect fine scale physiological changes associated with estrus, we analyzed changes in fecal E1G (n = 62) and vaginal cytology (n = 157) 15 days before and after each female's single copulation event (Day = 0). Changes in fecal E1G had the highest accuracy at detecting Day = 0. Fecal E1G increased leading up to estrus, peaked at Day = 0, and then declined. Although we did observe the characteristic increase in superficial cells associated with impending estrus, the type of cell which peaked closest to Day = 0 was intermediate. The uncertainty around the peak in intermediate cells, indicating estrus, was greater than the uncertainty associated with detecting estrus from fecal E1G. Collectively, these results suggest that changes in fecal E1G and vaginal cytology are viable tools to detect estrus in Steller sea lions, but require daily sampling to detect gradual changes, limiting their applicability to studies of wild populations.

Juvenile Steller sea lion (Eumetopias jubatus) utilization distributions in the Gulf of Alaska.

BACKGROUND: A utilization distribution quantifies the temporal and spatial probability of space use for individuals or populations. These patterns in movement arise from individuals' internal state and from their response to the external environment, and thus can provide insights for assessing factors associated with the management of threatened populations. The Western Distinct Population Segment of the Steller sea lion (Eumetopias jubatus) has declined to approximately 20% of levels encountered 40 years ago. At the height of the decline, juvenile survival appeared to be depressed and currently there is evidence that juvenile mortality due to predation may be constraining recovery in some regions. Therefore, our objectives were to identify what spaces are biologically important to juvenile Steller sea lions in the Kenai Fjords and Prince William Sound regions of the Gulf of Alaska. METHODS: We examined geospatial location data from juvenile sea lions tagged between 2000 and 2014 (n = 84) and derived individual and pooled-population utilization distributions (UDs) from their movements. Core areas were defined from the UDs using an individual-based approach; this quantitatively confirmed that all individuals in our sample exhibited concentrated use within their home range (95% UD). Finally, we explored if variation in UD characteristics were associated with sex, season, age, or region. RESULTS: We found evidence that individual juvenile home ranges were region and sex-specific, with males having larger home ranges on average. Core space characteristics were also sex-specific, and exhibited seasonal patterns of reduced size, increased proximity to haulouts, and increased intensity of use in the summer, but only in the Kenai Fjords-Gulf of Alaska region. CONCLUSIONS: This study highlights the areas of biological importance during this vulnerable life history stage, and the demographic, seasonal, and spatial factors associated with variation in movement patterns for a marine mesopredator. This can be useful information for promoting species recovery, and for future efforts to understand ecological patterns such as predator-prey interactions.

Nicotine Lozenges in the Relief of Behaviorally Provoked Craving.

OBJECTIVES: Environmental cues may precipitate nicotine cravings in smokers. We present 2 studies exploring the efficacy of nicotine mini lozenges to reduce nicotine craving in smokers following behavioral provocation. METHODS: Healthy smokers aged ≥18 years enrolled. In Study 1, participants were stratified by number of cigarettes smoked daily; Study 2 enrolled only heavy smokers. After an abstinence period, participants engaged in behavioral provocation to induce nicotine craving before receiving a nicotine mini lozenge (Study 1: 1.5 mg or 4 mg; Study 2: 4 mg) or matching placebo. Craving was assessed using a 100-mm visual analogue scale, and safety was monitored. RESULTS: In Study 1, neither nicotine mini lozenge dose significantly reduced craving in smokers versus placebo. In Study 2, 4-mg nicotine mini lozenges significantly reduced craving scores 5 minutes post-treatment (least-square mean [LSM] change from baseline: -41.8; 95% confidence interval [CI]: -45.8, -37.7) versus placebo (-25.9; 95% CI: -30.0, -21.8; p < .001). Adverse events were infrequent, mild in intensity, and more common with the 4-mg nicotine mini lozenges. CONCLUSIONS: Behaviorally provoked nicotine craving can be significantly and safely reduced in heavy/high-dependency smokers with 4-mg nicotine mini lozenges.

Corkscrew Seals: Grey Seal (Halichoerus grypus) Infanticide and Cannibalism May Indicate the Cause of Spiral Lacerations in Seals.

Large numbers of dead seals with characteristic spiral lesions have been washing ashore around the North Atlantic over the past two decades. Interactions with ship propellers and shark predation have been suggested as the likely causal mechanisms. However, new evidence points towards a more likely candidate: grey seal predation. An adult male grey seal was observed and recorded catching, killing and eating five weaned grey seal pups over a period of one week on the Isle of May, Scotland. A further 9 carcasses found in the same area exhibited similar injuries. Post mortem analysis of lesions indicated the wound characteristics were similar to each other and in 12 of the 14 carcasses analysed, were indistinguishable from carcasses previously attributed to propeller interaction. We therefore propose that most of the seal carcasses displaying spiral lacerations in the UK are caused by grey seal predation. Cases in other locations should be re-evaluated using the scoring system presented here to identify whether grey seal predation is a major cause of mortality in phocid seals.

Novel exposure biomarkers of N,N-diethyl-m-toluamide (DEET): Data from the 2007-2010 National Health and Nutrition Examination Survey.

BACKGROUND: N,N-diethyl-m-toluamide (DEET) is a widely used insect repellent in the United States. OBJECTIVES: To assess exposure to DEET in a representative sample of persons 6years and older in the U.S. general population from the 2007-2010 National Health and Nutrition Examination Survey. METHODS: We analyzed 5348 urine samples by using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used regression models to examine associations of various demographic parameters with urinary concentrations of DEET biomarkers. RESULTS: We detected DEET in ~3% of samples and at concentration ranges (>0.08µg/L-45.1µg/L) much lower than those of 3-(diethylcarbamoyl)benzoic acid (DCBA) (>0.48µg/L-30,400µg/L) and N,N-diethyl-3-hydroxymethylbenzamide (DHMB) (>0.09µg/L-332µg/L). DCBA was the most frequently detected metabolite (~84%). Regardless of survey cycle and the person's race/ethnicity or income, adjusted geometric mean concentrations of DCBA were higher in May-Sep than in Oct-Apr. Furthermore, non-Hispanic whites in the warm season were more likely than in the colder months [adjusted odds ratio (OR)=10.83; 95% confidence interval (CI), 3.28-35.79] and more likely than non-Hispanic blacks (OR=3.45; 95% CI, 1.51-7.87) to have DCBA concentrations above the 95th percentile. CONCLUSIONS: The general U.S. population, including school-age children, is exposed to DEET. However, reliance on DEET as the sole urinary biomarker would likely underestimate the prevalence of exposure. Instead, oxidative metabolites of DEET are the most adequate exposure biomarkers. Differences by season of the year based on demographic variables including race/ethnicity likely reflect different lifestyle uses of DEET-containing products.

Polyketides from an Endophytic Aspergillus fumigatus Isolate Inhibit the Growth of Mycobacterium tuberculosis and MRSA.

The crude extract of Aspergillusfumigatus isolate AF3-093A, an endophyte of the brown alga Fucus vesiculosus, showed significant antimicrobial activity in initial bioactivity screens. Bioassay-guided fractionation of the extract led to the isolation of flavipin, chaetoglobosin A and chaetoglobosin B, all of which inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus and Mycobacterium tuberculosis H37Ra. The antimycobacterial activity of these compounds has not been previously reported.

Isolation of (-)-avenaciolide as the antifungal and antimycobacterial constituent of a Seimatosporium sp. Endophyte from the medicinal plant Hypericum perforatum .

An extract of Seimatosporium sp., an endophyte from the Canadian medicinal plant Hypericum perforatum, exhibited significant antifungal and antimycobacterial activity against Candida albicans and Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation led to the isolation of (-)-avenaciolide as the only bioactive constituent of the extract. This is the first report of both the antimycobacterial activity of avenaciolide and its isolation from a Seimatosporium sp. fungus.

On-line solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry approach to quantify N,N-diethyl-m-toluamide and oxidative metabolites in urine.

Human exposure to N,N-diethyl-m-toluamide (DEET) occurs because of the widespread use of DEET as an active ingredient in insect repellents. However, information on the extent of such exposure is rather limited. Therefore, we developed a fast on-line solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry (HPLC-MS/MS) method to measure in urine the concentrations of DEET and two of its oxidative metabolites: N,N-diethyl-3-(hydroxymethyl)benzamide and 3-(diethylcarbamoyl)benzoic acid (DCBA). To the best of our knowledge, this is the first HPLC-MS/MS method for the simultaneous quantification of DEET and its select metabolites in human urine. After enzymatic hydrolysis of the conjugated species in 0.1 mL of urine, the target analytes were retained and pre-concentrated on a monolithic column, separated from each other and from other urinary biomolecules on a reversed-phase analytical column, and detected by atmospheric pressure chemical ionization in positive ion mode. The limits of detection ranged from 0.1 ng mL(-1) to 1.0 ng mL(-1), depending on the analyte. Accuracy ranged between 90.4 and 104.9%, and precision ranged between 5.5 and 13.1% RSD, depending on the analyte and the concentration. We tested the usefulness of this method by analyzing 75 urine samples collected anonymously in the Southeastern United States in June 2012 from adults with no known exposure to DEET. Thirty eight samples (51%) tested positive for at least one of the analytes. We detected DCBA most frequently and at the highest concentrations. Our results suggest that this method can be used for the analysis of a large number of samples for epidemiological studies to assess human exposure to DEET.

Quantification of riboflavin in human urine using high performance liquid chromatography-tandem mass spectrometry.

We developed a selective method to measure riboflavin in human urine. Sample preparation involved solid phase extraction and concentration of the target analyte in urine. The urine concentrate was analyzed using high performance liquid chromatography-tandem mass spectrometry. Riboflavin concentrations were quantified using an isotopically labeled internal standard. The limit of detection was 11 ng/mL, and the linear range was 4.4-20,000 ng/mL. The relative standard deviation at 100, 1000, and 5000 ng/mL was 17%, 17%, and 12%, respectively. The accuracy was 90%. On average, 100 samples, including calibration standards and quality control samples, were prepared per day. Using our method, we measured concentrations of riboflavin in human urine samples that were collected from participants in a study where riboflavin was used as a surrogate chemical to simulate exposure to an environmental toxicant.

How black African and white British women perceive depression and help-seeking: a pilot vignette study.

BACKGROUND: The detection of psychological problems of black African people has been found to be substantially lower, compared with white British and black Caribbean people. This may be due to differences in patients' perceptions of illness. Little research has been carried out on factors that may influence the help-seeking behaviour of black Africans. AIMS: To assess differences in the perceptions of depression of black African and white British women that may influence lower detection and to investigate whether there are ethnic group differences in reasons for not seeking formal help. METHODS: A short quantitative illness perception measure, the Brief Illness Perception Questionnaire (BIPQ), was used in a community survey, using a standard text vignette methodology to control for variations in previous experiences of depression. Responses from women who indicated that they would not seek formal help for depressive symptoms were qualitatively analyzed. RESULTS: Differences in perceptions of depression were found between black African (n = 73) and white British groups (n = 72) on five of the nine BIPQ dimensions. Black women were more likely to perceive depression to have less serious consequences; to be associated with fewer symptoms; to be less chronic; to be less amenable to treatment; and more frequently attributed depression to social factors. Over half the participants (n = 74) said they would not seek formal help for depressive symptoms. Six qualitative response categories emerged to explain non-consultation. The most common factor for both groups related to GP consultation difficulties. Significantly more white women cited preferring alternative help sources as a reason for non-consultation. The greater number of black women citing anti-medication beliefs was marginally significant. There were no differences between the ethnic groups in their use of the remaining three categories: illness characteristics; service constraints; and stigma/shame. CONCLUSION: Differing perceptions of depression among black and white women could help explain GPs' lower detection rates of depressive problems of black women. Differences in views about the formal help available may explain ethnic differences in help-seeking.

Compatibility of ceftobiprole medocaril with selected drugs during simulated Y-site administration.

PURPOSE: The physical compatibility of the new cephalosporin ceftobiprole medocaril with 70 other drugs during simulated Y-site injection was studied. METHODS: Ceftobiprole was reconstituted with sterile water for injection. Dilutions of ceftobiprole 2 mg/mL (as ceftobiprole medocaril 2.67 mg/mL) were prepared in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection. For testing compatibility with the other drugs, a 5-mL sample of the ceftobiprole 2-mg/mL admixtures was combined with a 5-mL sample of the other drug either undiluted or diluted with one of the three vehicles. Each combination was prepared in duplicate, switching the order of drug addition, and kept at room temperature. At intervals up to four hours after preparation, samples were examined visually and with the aid of a Tyndall beam and measured with a turbidimeter and a particle sizer and counter. Compatibility with propofol was evaluated by checking for emulsion separation and particles after centrifugation. RESULTS: In all three vehicles, ceftobiprole was compatible with 31 other drugs and incompatible with 32. With 7 drugs, compatibility was dependent on the vehicle used. Signs of incompatibility included the presence of visible and subvisible particles, haze, and turbidity. No incompatibilities were related to the order of mixing. CONCLUSION: Of the 70 drugs evaluated for compatibility with ceftobiprole 2 mg/ mL (as medocaril) in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection, 31 were found to be compatible and 32 were found to be incompatible in all three of the infusion solutions. For 7 of the drugs, compatibility was dependent on which infusion solution was used. Ceftobiprole medocaril should not be simultaneously administered via a Y site with drugs with which it was shown to be incompatible.

Human CD8 responses to a complete epitope set from preproinsulin: implications for approaches to epitope discovery.

PURPOSE: In this study, we explored the breadth of CD8 T cell reactivity to preproinsulin (PPI) in type 1 diabetes. MATERIALS AND METHODS: We tested a complete peptide set in pools covering all 406 potential 8-11mer epitopes of PPI and 61 algorithm-predicted human leukocyte antigen (HLA)-A2-specific epitopes (15 pools) from islet-specific glucose-6-phophatase catalytic subunit-related protein (IGRP), using a CD8-specific granzyme B enzyme-linked immunosorbent spot assay. RESULTS: Responses were seen to 64 of the 102 PPI pools in two or more newly diagnosed patients (63%) compared to 11 pools in the control subjects (11%, p < 0.0001, Fisher's exact test). We identified five pools containing 20 peptides, which distinguished patients from control subjects, most of which had predicted low-affinity binding to HLA class I molecules. In contrast, fewer (5 of 15 = 33%) IGRP peptide pools, selected by higher binding affinity for HLA-A2 (present in seven of eight patients and five of seven control subjects), stimulated responses in two or more patients, and none stimulated responses in more than two control subjects (p = 0.042, Fisher's exact test). CONCLUSION: Thus, we conclude that CD8 T cell reactivity to PPI in patients with type 1 diabetes can be much broader than shown previously and more diverse than seen in control subjects. Furthermore, responses were often stimulated by peptides with low predicted HLA-binding affinities.

Concentrations of xenobiotic chemicals in the maternal-fetal unit.

Exposure to a variety of toxic chemicals has been associated with adverse health outcomes. Presumably, the most vulnerable population for these adverse health outcomes are fetuses that are exposed to toxicants in utero. Fetuses have immature organ systems and often their detoxification enzymes or enzymatic processes are not fully developed when exposures occur. Many xenobiotic chemicals have been shown to pass through the placental barrier and into the fetal blood stream. These exposures have been associated with adverse birth outcomes, neurocognitive delays and adult onset disease. Exposures associated with interuterine growth retardation have been linked to a variety of adult onset diseases such as coronary artery disease and diabetes. In this article, we review a variety of chemicals that have been known to enter the fetal environment and their potential to affect both early childhood and subsequently adult health. We restrict our review to chemicals shown to be present in umbilical cord blood, amniotic fluid, or meconium, thus unequivocally demonstrating the chemicals have entered the fetal environment. In some instances where known health outcomes have occurred from these exposures, we note these and any caveats associated with the exposures.

Does changing the order of threat and efficacy information influence the persuasiveness of threat messages?

OBJECTIVES: The aim of this study is to investigate the impact of changing the conventional threat-before-efficacy order of threat messages on the persuasiveness of a leaflet informing women smokers of the link between smoking and cervical cancer. DESIGN: The study used a between-groups design in which women smokers were sequentially allocated to one of three groups. Two groups received one of two leaflets aimed at providing information about the link between smoking and cervical cancer: one provided threat-before-efficacy information; the other provided efficacy-before-threat information. The third group received no leaflet. METHODS: Participants (N=178) were recruited by a commercial survey organization. Purposeful sampling was used to ensure that women with a wide range of ages and educational qualifications were included. Outcomes were intention to stop smoking, recall of information, and threat and efficacy perceptions. RESULTS: Although women in the 'efficacy-before-threat' group recalled more efficacy information, and those in the 'threat-before-efficacy' group recalled more threat information, the leaflets were similarly persuasive. Compared with women not given a leaflet, those given either of the two leaflets had greater intentions to stop smoking and higher threat and efficacy perceptions. CONCLUSIONS: Informing women of the link between smoking and cervical cancer increases their intentions to stop smoking. Changing the order of threat and efficacy information does not influence the persuasiveness of this message. Order effects may be more likely in experimental contexts using weaker messages or those that are not novel.

Hyperimmunoglobulin E syndrome: two cases and a review of the literature.

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cases seen at our institution and review the current literature. Patient 1 was an 18-month-old African American boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He had severely eczematous skin, ultimately complicated by eczema herpeticum. After treatment of systemic infections with culture-directed antibiotics, a brief course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15-year-old Caucasian boy with long-standing HIES. He has been maintained on a regimen of interferon gamma injections given 3 times weekly and monthly intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics, and low-dose fluconazole. He has occasional episodes of cold abscesses and sinusitis, but has had excellent control since institution of this regimen and has not experienced any adverse effects.

A comparison of Australian and UK obstetricians' and midwives' preferences for screening tests for Down syndrome.

OBJECTIVE: To establish and compare obstetricians' and midwives' preferences for hypothetical prenatal screening tests for Down syndrome. METHODS: A cross-sectional questionnaire survey was completed by 296 obstetricians and midwives at two teaching hospitals: one in Melbourne, Australia (n = 175), and one in London, UK (n = 94). Conjoint analysis was undertaken using random effects probit regression. RESULTS: No significant differences were seen in any measurements when comparing obstetricians in Australia and the UK or midwives in Australia and the UK. Obstetricians and midwives shared similar relative values regarding the importance of the detection rate of the screening tests. However, obstetricians placed higher relative values on both timing of prenatal tests and risk associated with the subsequent diagnostic test than did midwives when considering optimal tests to offer women. Marginal rates of substitution suggest that, compared with midwives, obstetricians would wait longer and accept a greater decrease in detection rate for a test if it was safer. Younger midwives placed higher value on both detection rate and safety of prenatal tests than older midwives. Female obstetricians placed higher value on the timing of a test than male obstetricians. CONCLUSION: Obstetricians in Australia and UK placed almost identical importance on test attributes, as did the midwives in the two countries. However, different attitudes towards tests were seen between obstetricians and midwives.