Implementation Evaluation of a Complex Intervention to Improve Timeliness of Care for Veterans with Transient Ischemic Attack.

BACKGROUND: The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurologic Symptoms (PREVENT) program was designed to address systemic barriers to providing timely guideline-concordant care for patients with transient ischemic attack (TIA). OBJECTIVE: We evaluated an implementation bundle used to promote local adaptation and adoption of a multi-component, complex quality improvement (QI) intervention to improve the quality of TIA care Bravata et al. (BMC Neurology 19:294, 2019). DESIGN: A stepped-wedge implementation trial with six geographically diverse sites. PARTICIPANTS: The six facility QI teams were multi-disciplinary, clinical staff. INTERVENTIONS: PREVENT employed a bundle of key implementation strategies: team activation; external facilitation; and a community of practice. This strategy bundle had direct ties to four constructs from the Consolidated Framework for Implementation Research (CFIR): Champions, Reflecting & Evaluating, Planning, and Goals & Feedback. MAIN MEASURES: Using a mixed-methods approach guided by the CFIR and data matrix analyses, we evaluated the degree to which implementation success and clinical improvement were associated with implementation strategies. The primary outcomes were the number of completed implementation activities, the level of team organization and > 15 points improvement in the Without Fail Rate (WFR) over 1 year. KEY RESULTS: Facility QI teams actively engaged in the implementation strategies with high utilization. Facilities with the greatest implementation success were those with central champions whose teams engaged in planning and goal setting, and regularly reflected upon their quality data and evaluated their progress against their QI plan. The strong presence of effective champions acted as a pre-condition for the strong presence of Reflecting & Evaluating, Goals & Feedback, and Planning (rather than the other way around), helping to explain how champions at the +2 level influenced ongoing implementation. CONCLUSIONS: The CFIR-guided bundle of implementation strategies facilitated the local implementation of the PREVENT QI program and was associated with clinical improvement in the national VA healthcare system. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338.

Mental health and wellbeing coordinators in primary schools to support student mental health: protocol for a quasi-experimental cluster study.

BACKGROUND: Half of mental health disorders begin before the age of 14, highlighting the importance of prevention and early-intervention in childhood. Schools have been identified globally by policymakers as a platform to support good child mental health; however, the majority of the research is focused on secondary schools, with primary schools receiving very little attention by comparison. The limited available evidence on mental health initiatives in primary schools is hindered by a lack of rigorous evaluation. This quasi-experimental cluster study aims to examine the implementation and effectiveness of a Mental Health and Wellbeing Co-ordinator role designed to build mental health capacity within primary schools. METHODS: This is a primary (ages 5-12) school-based cluster quasi-experimental study in Victoria, Australia. Before baseline data collection, 16 schools selected by the state education department will be allocated to intervention, and another 16 matched schools will continue as 'Business as Usual'. In intervention schools, a mental health and well-being coordinator will be recruited and trained, and three additional school staff will also be selected to receive components of the mental health training. Surveys will be completed by consenting staff (at 2-, 5-, 10- and 17-months post allocation) and by consenting parents/carers (at 3-, 10- and 17-months post allocation) in both intervention and business as usual schools. The primary objective is to assess the change in teacher's confidence to support student mental health and wellbeing using the School Mental Health Self-Efficacy Teacher Survey. Secondary objectives are to assess the indirect impact on systemic factors (level of support, prioritisation of child mental health), parent and teachers' mental health literacy (stigma, knowledge), care access (school engagement with community-based services), and student mental health outcomes. Implementation outcomes (feasibility, acceptability, and fidelity) and costs will also be evaluated. DISCUSSION: The current study will examine the implementation and effectiveness of having a trained Mental Health and Wellbeing Coordinator within primary schools. If the intervention increases teachers' confidence to support student mental health and wellbeing and builds the capacity of primary schools it will improve student mental health provision and inform large-scale mental health service reform. TRIAL REGISTRATION: The trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) on July 6, 2021. The registration number is ACTRN12621000873820 .

The protocol-guided rapid evaluation of veterans experiencing new transient neurological symptoms (PREVENT) quality improvement program: rationale and methods.

BACKGROUND: Transient ischemic attack (TIA) patients are at high risk of recurrent vascular events; timely management can reduce that risk by 70%. The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) developed, implemented, and evaluated a TIA quality improvement (QI) intervention aligned with Learning Healthcare System principles. METHODS: This stepped-wedge trial developed, implemented and evaluated a provider-facing, multi-component intervention to improve TIA care at six facilities. The unit of analysis was the medical center. The intervention was developed based on benchmarking data, staff interviews, literature, and electronic quality measures and included: performance data, clinical protocols, professional education, electronic health record tools, and QI support. The effectiveness outcome was the without-fail rate: the proportion of patients who receive all processes of care for which they are eligible among seven processes. The implementation outcomes were the number of implementation activities completed and final team organization level. The intervention effects on the without-fail rate were analyzed using generalized mixed-effects models with multilevel hierarchical random effects. Mixed methods were used to assess implementation, user satisfaction, and sustainability. DISCUSSION: PREVENT advanced three aspects of a Learning Healthcare System. Learning from Data: teams examined and interacted with their performance data to explore hypotheses, plan QI activities, and evaluate change over time. Learning from Each Other: Teams participated in monthly virtual collaborative calls. Sharing Best Practices: Teams shared tools and best practices. The approach used to design and implement PREVENT may be generalizable to other clinical conditions where time-sensitive care spans clinical settings and medical disciplines. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338 [May 11, 2016].

A morphometric signature of depressive symptoms in unmedicated patients with mood disorders.

OBJECTIVE: A growing literature indicates that unipolar depression and bipolar depression are associated with alterations in grey matter volume. However, it is unclear to what degree these patterns of morphometric change reflect symptom dimensions. Here, we aimed to predict depressive symptoms and hypomanic symptoms based on patterns of grey matter volume using machine learning. METHOD: We used machine learning methods combined with voxel-based morphometry to predict depressive and self-reported hypomanic symptoms from grey matter volume in a sample of 47 individuals with unmedicated unipolar and bipolar depression. RESULTS: We were able to predict depressive severity from grey matter volume in the anteroventral bilateral insula in both unipolar depression and bipolar depression. Self-reported hypomanic symptoms did not predict grey matter loss with a significant degree of accuracy. DISCUSSION: The results of this study suggest that patterns of grey matter volume alteration in the insula are associated with depressive symptom severity across unipolar and bipolar depression. Studies using other modalities and exploring other brain regions with a larger sample are warranted to identify other systems that may be associated with depressive and hypomanic symptoms across affective disorders.

Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility.

Epigenetic modifications in histones are crucial for proper sperm physiology, egg activation and reproductive development of males. The objectives of this study were to determine the conservation and interactomes of histone three (H3) and ascertain the expression dynamics of acetylated and methylated H3 lysine 27 (H3K27ac and H3K27me3) in spermatozoa from Holstein bulls with different fertility. Methods in immunocytochemistry and flow cytometry were used to evaluate the expression dynamics of H3K27ac and H3K27me3 in spermatozoa from 10 bulls with different in vivo fertility. Computational biology methods including Clustal Omega and Cytoscape were performed to determine the evolutionary conservation and interactome of H3. The post-translational modifications (PTM) of H3 (H3K27ac and H3K27me3) had different spatiotemporal dynamics in the sperm head. Intensities of methylation were higher than those of acetylation and inversely correlated between the two fertility groups (p = .0032). The interacting proteins of H3 are involved in critical subcellular processes such as regulation of methylation, nucleosome assembly, regulation of DNA replication and chromatin assembly. These results are significant because they help advance fundamental science and biotechnology of mammalian reproduction.

Black holes in higher derivative gravity.

Extensions of Einstein gravity with higher-order derivative terms arise in string theory and other effective theories, as well as being of interest in their own right. In this Letter we study static black-hole solutions in the example of Einstein gravity with additional quadratic curvature terms. A Lichnerowicz-type theorem simplifies the analysis by establishing that they must have vanishing Ricci scalar curvature. By numerical methods we then demonstrate the existence of further black-hole solutions over and above the Schwarzschild solution. We discuss some of their thermodynamic properties, and show that they obey the first law of thermodynamics.

Hope and the use of behavioural strategies related to diet and physical activity.

BACKGROUND: The use of specific behavioural strategies such as portion control or meal planning is important for weight management, although studies of determinants of strategy use are limited. The present study explored the concept of hope and its association with the use of behavioural strategies. METHODS: Data were obtained from a larger cross-sectional survey conducted in 2009 among 178 patients of a city-county sponsored primary care clinic in the Midwest region of the USA. Hope was measured with subscales representing 'agency' (determination in meeting goals) and 'pathways' (perception of ways to meet goals) and a total score. Diet and physical activity-related strategies were captured with five and two scales, respectively. RESULTS: Analyses showed a significant (P < 0.05) association between both the total hope score and the agency subscale and all behavioural strategy measures. The pathways subscale was significantly associated with physical activity-related strategies, and a subset of diet-related strategies. CONCLUSIONS: The hope measures should be explored further in the context of a weight loss intervention to determine their predictive association with the use of specific behavioural strategies.

Comparison of the epidemiology of acne vulgaris among Caucasian, Asian, Continental Indian and African American women.

BACKGROUND: Acne vulgaris is a common skin disease with a large quality of life impact, characterized by comedones, inflammatory lesions, secondary dyspigmentation and scarring. There are few large objective studies comparing acne epidemiology between racial and ethnic groups. OBJECTIVE: This study aimed to define the prevalence and subtypes of acne in women of different racial groups from four ethnicities. METHODS: The sample consisted of 2895 (384 African American, 520 Asian, 1295 Caucasian, 258 Hispanic and 438 Continental Indian) women ranging in age from 10 to 70 years. Photographs of subjects were graded for acne lesions, scars, dyspigmentation, and measurements taken of sebum excretion and pore size. RESULTS: Clinical acne was more prevalent in African American and Hispanic women (37%, 32% respectively) than in Continental Indian, Caucasian and Asian (23%, 24%, 30% respectively) women. All racial groups displayed equal prevalence of both subtypes of acne with the exception of Asians, for whom inflammatory acne was more prevalent than comedonal (20% vs. 10%) acne, and in Caucasians, for whom comedonal acne was more prevalent than inflammatory (14% vs. 10%) acne. Hyperpigmentation was more prevalent in African American and Hispanic (65%, 48% respectively) than in Asian, Continental Indian and Caucasian (18%, 10%, 25% respectively) women. Dyspigmentation and atrophic scarring were more common in African American and Hispanic women than in all other ethnicities. There was a negative correlation between pore size and skin lightness for all ethnicities. Sebum production was positively correlated with acne severity in African American, Asian and Hispanic women, and pore size was positively correlated with acne in African American, Asian and Continental Indian women, (for all above results, P<0.05). LIMITATIONS: Only female participants were recruited. Data collection was restricted to four cities, with some ethnicities from single cities. Acne was evaluated only on the left side of the face and the two-dimensional nature of photography may not capture all skin surface changes. CONCLUSION: Acne prevalence and sequelae were more common in those with darker skin types, suggesting that acne is a more heterogeneous condition than previously described and highlight the importance of skin-colour tailored treatment.

Comparison of lateral thermal spread using monopolar and bipolar diathermy, the Harmonic Scalpel and the Ligasure.

BACKGROUND: Electrosurgery for dissection and haemostasis should be associated with minimal thermal spread to surrounding tissues. This study investigated lateral thermal spread following ex vivo application of four commonly utilized instruments. METHODS: Monopolar and bipolar diathermy (power settings 20, 30 and 40 W), the Harmonic Scalpel and Ligasure (power settings 1, 3 and 5) were studied after application to standardized porcine muscle cuts for 5, 10 or 15 s. Temperatures generated at the tips of the instruments, in the tissues adjacent to the tips and 1 cm away were recorded. RESULTS: Following a 5-s application at the highest power setting, the highest mean(s.d.) temperatures recorded at the tips of monopolar and bipolar diathermy, Harmonic Scalpel and Ligasure instruments were 78.9(4.1), 41.9(2.2), 47.6(2.5) and 44.2(2.6) degrees C respectively. Temperatures at the instrument tips after use for 15 s remained above 42 degrees C for 55, 25, 15 and 15 s respectively. Applying monopolar diathermy (10 s at 40 W) resulted in a temperature recording of 59.2(2.2) degrees C in tissues 1 cm away from the tip of the instrument. CONCLUSION: The degree of lateral thermal spread varied with instrument type, power setting and application time. Monopolar diathermy resulted in the highest temperatures and the greatest degree of thermal spread in tissues.

A new maneuver for endotracheal tube insertion during difficult GlideScope intubation.

BACKGROUND: The GlideScope Video Laryngoscope (Verathon, Bothell, WA) is a video laryngoscopy system that can be used for routine intubation, but is also commonly used as an alternative for difficult or failed airways. Previous reports have identified a very high incidence of grade 1 and grade 2 Cormack-Lehane glottic views, but despite these high-grade views, intubation is sometimes difficult due to the angle of insertion and shape of the endotracheal tube. Several maneuvers have been reported to increase the likelihood of successful endotracheal tube placement in these uncommon cases of failure. CASE REPORT: We report the case of a patient who could not be intubated with the GlideScope despite an easily obtained grade 1 laryngoscopic view. The impediment to intubation was identified as a sharp angulation of the trachea with respect to the larynx, such that the trachea formed a steep posterior angle with the laryngeal/glottic axis. Intubation was achieved using a previously unreported maneuver, in which the endotracheal tube with a sharply curved malleable stylet was inserted through the glottis, and then rotated 180 degrees to permit passage down the trachea. DISCUSSION AND CONCLUSION: We believe that this maneuver may be useful in other cases of failed GlideScope intubation, when a high-grade laryngeal view is obtained but tube passage is not possible due to a sharp posterior angulation of the trachea.

Study of X-ray field junction dose using an a-Si electronic portal imaging device.

Field junctions between megavoltage photon beams are important in modern radiotherapy for treatments such as head and neck and breast cancer. An electronic portal imaging device (EPID) may be used to study junction dose between two megavoltage X-ray fields. In this study, the junction dose was used to determine machine characteristics such as jaw positions and their reproducibility, collimator rotation and the effect of gantry rotation. All measurements were done on Varian linear accelerators with EPID (Varian, Palo Alto, CA). The results show reproducibility in jaw positions of approximately 0.3 mm for repeated jaw placement while EPID readings were reproducible within a standard deviation of 0.4% for fixed jaw positions. Junction dose also allowed collimator rotation error of 0.1 degrees to be observed. Dependence of junction dose on gantry rotation due to gravity was observed; the gravity effect being maximum at 180 degrees gantry angle (beam pointing up). EPIDs were found to be reliable tools for checking field junctions, which in turn may be used to check jaw reproducibility and collimator rotation of linacs.

Fronto-temporal galanin modulates impulse control.

RATIONALE: The neuropeptide galanin has been implicated in a wide range of pathological conditions in which frontal and temporal structures are compromised. It works through three subtypes of G-protein-coupled receptors. One of these, the galanin receptor 1 (Gal-R1) subtype, is densely expressed in the ventral hippocampus (vHC) and ventral prefrontal cortex (vPFC); two brain structures that have similar actions on behavioral control. We hypothesize that Gal-R1 contributes to cognitive-control mechanisms that require hippocampal-prefrontal cortical circuitry. OBJECTIVE: To examine the effect of local vHC and vPFC infusions of M617, a Gal-R1 agonist, on inhibitory mechanisms of response control. METHODS: Different cohorts of rats were implanted with bilateral guide cannulae targeting the vPFC or the vHC. Following infusion of the Gal-R1 agonist, we examined the animals' behavior using a touchscreen version of the 5-choice reaction time task (5-choice task). RESULTS: The Gal-R1 agonist produced opposing behaviors in the vPFC and vHC, leading to disruption of impulse control when infused in the vPFC but high impulse control when infused into the vHC. This contrast between areas was accentuated when we added variability to the timing of the stimulus, which led to long decision times and reduced accuracy in the vPFC group but a general improvement in performance accuracy in the vHC group. CONCLUSIONS: These results provide the first evidence of a selective mechanism of Gal-R1-mediated modulation of impulse control in prefrontal-hippocampal circuitry.

A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome.

STUDY OBJECTIVE: To evaluate the efficacy and tolerability of XP13512/ GSK1838262, an investigational nondopaminergic agent for the treatment of moderate-to-severe primary restless legs syndrome (RLS). DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Nine US clinical sites. PATIENTS: Thirty-eight treatment-naive subjects with RLS (mean +/- SD age 50.1 +/- 13.2 years). INTERVENTIONS: XP13512 1800 mg/day followed by placebo or placebo followed by XP13512 1800 mg/day for 14 days, with a 7-day washout between treatment periods. MEASUREMENTS AND RESULTS: The primary endpoint was mean change from baseline International RLS Study Group rating scale (IRLS) total score on Day 14, analyzed using analysis of variance with sequence, period, and treatment as fixed effects and subjects within sequence as a random effect. XP13512 significantly reduced IRLS total score on Day 14 compared with placebo (mean +/- SD: XP13512 -12.1 +/-6.5, placebo -1.9 +/- 6.3; P < 0.0001). Polysomnographic data showed that XP13512 significantly improved sleep architecture on Day 14 compared with placebo (mean +/- SD change from baseline sleep time [minutes]: stage 1: XP13512 -9.8 +/- 23.9, placebo 0.4 +/-23.2; adjusted P<0.0054, nominal P<0.0001; stage 3/4 (slow-wave sleep): XP13512 22.8 +/- 40.8, placebo 1.4 +/- 34.3; adjusted P=0.0092, nominal P=0.0002). The most frequently reported adverse events were somnolence (XP13512 30.6%, placebo 2.8%) and dizziness (XP13512 27.8%, placebo 5.6%). CONCLUSIONS: XP13512 1800 mg/day significantly reduced RLS symptoms, improved sleep, and was generally well tolerated in subjects with moderate-to-severe primary RLS across 14 days of treatment.

A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator.

The human immunodeficiency virus (HIV) tat protein (Tat) is a positive regulator of virus gene expression and replication. Biotinylated Tat was used as a probe to screen a lambda gt11 fusion protein library, and a complementary DNA encoding a protein that interacts with Tat was cloned. Expression of this protein, designated TBP-1 (for Tat binding protein-1), was observed in a variety of cell lines, with expression being highest in human cells. TBP-1 was localized predominantly in the nucleus, which is consistent with the nuclear localization of Tat. In cotransfection experiments, expression of TBP-1 was able to specifically suppress Tat-mediated transactivation. The strategy described may be useful for direct identification and cloning of genes encoding proteins that associate with other proteins to modulate their activity in a positive or negative fashion.

A global role for zebrafish klf4 in embryonic erythropoiesis.

There are two waves of erythropoiesis, known as primitive and definitive waves in mammals and lower vertebrates including zebrafish. The founding member of the Kruppel-like factor (KLF) family of CACCC-box binding proteins, EKLF/Klf1, is essential for definitive erythropoiesis in mammals but only plays a minor role in primitive erythropoiesis. Morpholino knockdown experiments have shown a role for zebrafish klf4 in primitive erythropoiesis and hatching gland formation. In order to generate a global understanding of how klf4 might influence gene expression and differentiation, we have performed expression profiling of klf4 morphants, and then performed validation of many putative target genes by qRT-PCR and whole mount in situ hybridization. We found a critical role for klf4 in embryonic globin, heme synthesis and hatching gland gene expression. In contrast, there was an increase in expression of definitive hematopoietic specific genes such as larval globin genes, runx1 and c-myb from 24 hpf, suggesting a selective role for klf4 in primitive rather than definitive erythropoiesis. In addition, we show klf4 preferentially binds CACCC box elements in the primitive zebrafish beta-like globin gene promoters. These results have global implications for primitive erythroid gene regulation by KLF-CACCC box interactions.

Antioxidant gene expression in preeclamptic placentae: a preliminary investigation.

Oxidative stress has been implicated in the pathogenesis of preeclampsia. This study measured the relative mRNA expression of antioxidant proteins glutathione peroxidase 1 and 4, glutathione reductase, thioredoxin 1 and 2, thioredoxin reductase 1, thioredoxin peroxidase 3 and superoxide dismutase 1 and 2 in preeclamptic and non-preeclamptic placentae. Quantitative real-time PCR was conducted on placental mRNA isolated from preeclamptic and control patients. Cycle threshold numbers and fold differences were calculated as a measure of linear product amplification and used for comparison. The mRNA expression of glutathione reductase was significantly reduced (fold difference 0.41, p<0.05) in preeclamptic placenta when compared to controls while the expression of thioredoxin peroxidase 3 was significantly increased (fold difference 3.25, p<0.001) in the preeclamptic placentae. No significant difference in expression was observed for glutathione peroxidase 1 and 4, thioredoxin 1 and 2, thioredoxin reductase 1 and superoxide dismutase 1 and 2. These results suggest that it is the abnormal oxidative insult associated with preeclampsia not mRNA expression of antioxidant proteins that may be responsible for reduced antioxidant enzyme activity in preeclamptic placentae.

Determining the relationship between three-dimensional power Doppler data and true blood flow characteristics: an in-vitro flow phantom experiment.

OBJECTIVES: Three-dimensional (3D) ultrasound can be used to acquire power Doppler data which can be quantified to give an objective impression about blood flow within a tissue or organ. Proprietary software can be used to calculate three indices of vascularity: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Although these indices appear to have a predictive value in the clinical setting and can be shown to vary between different patient populations and over time within the same population, their relationship with true in-vivo blood flow characteristics has not been established. The objective was to examine the effect of flow rate, vessel number, attenuation and erythrocyte density on these indices. METHODS: A computer-driven flow phantom was used to continuously pump a nylon particle-based blood mimic (Orgasol(trade mark)) around a closed system through three different ultrasound test tanks. These tanks were designed specifically for these experiments and contained C-Flex(trade mark) tubing, in a variety of arrangements, encased in an agar-based tissue mimic. The test tanks were insonated with a modified 3D transvaginal 4-8-MHz ultrasound transducer and 3D power Doppler data were then acquired over a graduated series of flow rates, depths and blood mimic concentrations. Regression analysis was used to determine the resulting relationships. RESULTS: The VI increased linearly with an increase in flow rate (P < 0.05), whereas the FI increased in a cubic manner with a more rapid initial increase (P < 0.05). The VI demonstrated a similar linear increase with an increase in the erythrocyte mimic density (P < 0.05), whereas the FI increased markedly with a small change in erythrocyte mimic density and then plateaued (P < 0.01). There was a significant reduction in each index as the distance between the transducer and vessel increased (P < 0.05). Patterns similar to those seen in relation to the change in flow rate were evident, with a more linear relationship between depth and the VI and VFI than between depth and the FI, although the FI remained relatively constant and was not significantly affected by distance from the transducer until a depth of 55 mm was reached. Although a positive linear relationship was seen between vessel number and VI and VFI (P < 0.05) the FI demonstrated a very different and complex, cubic relationship (P < 0.001), increasing linearly until a maximum of three vessels were present when it decreased, and no overall correlation was seen (P > 0.05). CONCLUSIONS: The VI, FI and VFI are all significantly affected by volume flow, attenuation, vessel number and erythrocyte density, but in different ways. The VI and VFI seem to have a more predictable relationship, whereas the FI often demonstrates a more complex cubic relationship that is not always logical. Further work is required to establish the effect of other confounding parameters before valid conclusions may be made and a better understanding of 3D power Doppler ultrasound imaging achieved.

Evaluation of the effect of machine settings on quantitative three-dimensional power Doppler angiography: an in-vitro flow phantom experiment.

OBJECTIVES: Three-dimensional (3D) ultrasound is being used increasingly to acquire and subsequently quantify power Doppler data within the clinical setting. One proprietary software package calculates three 3D vascular indices: the vascularization index (VI), the flow index (FI), and the vascularization flow index (VFI). Our aim was to evaluate how different settings affect the Doppler signal in terms of its quantification by these three indices within a 3D dataset. METHODS: A computer-driven 'flow phantom' was used to continuously pump a nylon particle-based blood mimic (Orgasol(trade mark)) around a closed system through a C-flex(trade mark) tube embedded in an agar-based tissue mimic. The test tanks were insonated with a modified 3D transvaginal 4-8-MHz ultrasound transducer (V530D) and power Doppler data were acquired over a series of different settings. Each experiment involved the manipulation of just one Doppler setting in order to study it in isolation. RESULTS: As expected, all of the power Doppler settings, when altered, were found to effect significant changes (P < 0.05) in the VI, FI and VFI. The gain and signal power had the greatest effect, producing no Doppler signals at the lowest settings and the highest recordable indices at the maximum settings. The pulse repetition frequency (PRF) was the next most influential setting but a Doppler signal was seen and measurable at all of the different settings. The other Doppler settings had a much less profound effect on the vascular indices, with subtle but significantly different measures across the full range of settings. The speed of data acquisition was also found to affect the vascular indices, all of which were reduced when the fast mode was used although the only significant effect was on the VFI. CONCLUSIONS: The VI, FI and VFI are all affected significantly by variations in power Doppler settings and by the speed of acquisition. The gain and signal power have the greatest effect on the power Doppler signal, followed closely by the PRF. The other settings and speed of acquisition also influence the signal, but to a much lesser degree. It is essential to maintain Doppler settings if any meaningful comparisons are to be made within and between subjects.

Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4.

The four members of the ErbB family of receptor tyrosine kinases are involved in development and tumorigenesis of the mammary gland. Whereas the epidermal growth factor receptor, ErbB2 and ErbB3 are positively associated with various cancers, clinical studies of ErbB4 in breast cancer are contradictory. Results from tissue culture analyses and some clinical studies suggested that ErbB4 is either a tumor suppressor or is a negative regulator of ErbB2-driven tumors. Neu-Cre-ErbB4(flox/null) mice in which ErbB4 was inactivated by Cre-lox-mediated recombination in the mammary gland developed MMTV-Neu-driven mammary tumors with a similar latency period to mice with one or two wild-type ErbB4 alleles. Moreover, there was no difference in the histologies of tumors that developed, nor in the propensity to form lung metastases. Taken together these results suggest that ErbB4 is not a potent, highly penetrant tumor suppressor, nor is it a factor in Neu-mediated tumorigenesis in this model.