Search

Changes in sea level along the coastal southeastern United States (U.S.) influence the dynamic coastal response. In particular, the Southeast Coastal Network (SECN) of the National Park Service (NPS) has exhibited evidence of fluctuations in sea level which caused coastal erosion. Airborne LiDAR acquired from NOAA for Fort Matanzas National Monument, Fort Pulaski National Monument, Charles Pinckney National Historic Site, and Cape Lookout National Seashore were analyzed to identify changes in both elevation and the spatial volume of unconsolidated sedimentary material in the coastal southeast over time. Areas that exhibited an increase (deposited material) or decrease (eroded material) in elevation were mapped across the study area from 2006 to 2018. Results indicate a quasi-cyclic process where unconsolidated sediment distribution and the morphodynamic equilibrium changes with time. The coastal zones are steadily oscillating between the process of erosion and deposition affecting the coastal geomorphological dynamic. The use of LiDAR for evaluating coastal sustainability and resiliency due to this environmental phenomenon is clear.

This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population. Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL. Breath alcohol concentration was measured using the AlcoSense ™ Breathalyser on three separate visits. The primary end-point was the number of patients who were above the legal threshold for drink driving in Ireland. In total, 50 patients were recruited. 36 (68%) were female. The most common diagnosis was breast cancer (56%). Ten (20%) patients had metastatic disease and 4 (8%) had liver metastases. The mean paclitaxel dose administered was 118 mg. The mean amount of ethanol infused was 7.7 g. 27 patients had a detectable breath alcohol level on at least one visit. The mean breath alcohol concentration was 2 mcg/100 mL or 0.02 mg/L of breath. The maximum concentration of ethanol in exhaled breath was 11 mcg/100 mL or 0.11 mg/L which is 50% of the statutory limit for drink driving in Ireland. A weak correlation was observed between ethanol concentration in exhaled breath and the total amount of ethanol administered. Although no patient exceeded the general limit for drink driving in Ireland, three (6%) participants had a breath alcohol concentration above the threshold for professional, learner or novice drivers. Although definitive conclusions are limited by relatively small numbers, it seems unlikely that weekly paclitaxel infusions pose any significant risk to patients driving.

The influence of Ar+ ion irradiation on structural and nanomechanical properties of Yttria Stabilized Zirconia (YSZ) single crystals were studied. Specimens grown in three crystallographic orientations 〈1 0 0〉, 〈1 0 0〉 and 〈1 1 1〉 were irradiated at room temperature with 160 keV Ar-ions up to 3 fluences: 1 × 1014, 1 × 1015 and 1 × 1016 cm−2. Structural properties of the modified layers were measured by means of Grazing Incidence X-ray Diffraction (GI XRD) and Raman Spectroscopy techniques, whereas nanomechanical properties were asessed by using nanoindentation technique. Obtained results revealed shifts of the characteristic peaks and hardening effect in the function of Ar-ion fluence. Reported changes originate from at least two phenomena: (i) creation of radiation defects and (ii) local increase of stress induced by damage created by incoming ions – which magnitude may depend on crystallographic orientation.

Individuals occupying dominant and subordinate positions in social hierarchies exhibit divergent behaviours, physiology and neural functioning. Dominant animals express higher levels of dominance behaviours such as aggression, territorial defence and mate-guarding. Dominants also signal their status via auditory, visual or chemical cues. Moreover, dominant animals typically increase reproductive behaviours and show enhanced spatial and social cognition as well as elevated arousal. These biobehavioural changes increase energetic demands that are met via shifting both energy intake and metabolism and are supported by coordinated changes in physiological systems including the hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes as well as altered gene expression and sensitivity of neural circuits that regulate these behaviours. Conversely, subordinate animals inhibit dominance and often reproductive behaviours and exhibit physiological changes adapted to socially stressful contexts. Phenotypic changes in both dominant and subordinate individuals may be beneficial in the short-term but lead to long-term challenges to health. Further, rapid changes in social ranks occur as dominant animals socially ascend or descend and are associated with dynamic modulations in the brain and periphery. In this paper, we provide a broad overview of how behavioural and phenotypic changes associated with social dominance and subordination are expressed in neural and physiological plasticity.This article is part of the theme issue ‘The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies’.

Purpose The purpose of this study was to evaluate whether persons who stutter (PWS) reported benefits related to their stuttering and to describe the nature of those benefits. Method A mixed-methods approach was utilized. Qualitative content analysis was conducted with 5 different books, which included chapters written by PWS that focused on the experiences of stuttering and psychosocial aspects of the condition. In addition, 4 survey items measuring perceived benefits from stuttering were administered to 322 adults who stutter. Results Three major themes with 11 subthemes were identified in the qualitative analysis. PWS reported personal benefits from stuttering, including positive behavioral outcomes, cultivation of determination, feeling stronger, and emotional growth. Relationship benefits included social support access, deepening of relationships, and increased sensitivity to others. Changes in perspective included gained perspective about stuttering, gained perspective on life, a sense of appreciation, and finding positive meaning in challenges. Quantitative analysis revealed that over 90% of PWS agreed that stuttering has made them more understanding of other people, and over 80% agreed that it has made them stronger. Conclusion It is concluded that benefit finding among PWS should continue to be investigated in order to obtain a more complete understanding of the psychosocial aspects of stuttering and potentially to enhance therapeutic and support services for PWS.

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. Particularly, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor energetically inexpensive adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed an up-regulation of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed an up-regulation of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed up-regulation of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift energy investment in immune functioning and gene expression to match their contextual energetic demands.HighlightsImmunity is shaped by stress and energetic pressures associated with social statusDominant and subordinate mice favor adaptive and innate immunity, respectivelyDominants increase expression of genes involved in energy productionWound healing and DNA repair genes are upregulated in subordinatesGenes related to maintaining and signaling social status are upregulated in dominants

Social status is a critical factor determining health outcomes in human and nonhuman social species. In social hierarchies with reproductive skew, individuals compete to monopolize resources and increase mating opportunities. This can come at a significant energetic cost leading to trade-offs between different physiological systems. In particular, changes in energetic investment in the immune system can have significant short and long-term effects on fitness and health. We have previously found that dominant alpha male mice living in social hierarchies have increased metabolic demands related to territorial defense. In this study, we tested the hypothesis that high-ranking male mice favor adaptive immunity, while subordinate mice show higher investment in innate immunity. We housed 12 groups of 10 outbred CD-1 male mice in a social housing system. All formed linear social hierarchies and subordinate mice had higher concentrations of plasma corticosterone (CORT) than alpha males. This difference was heightened in highly despotic hierarchies. Using flow cytometry, we found that dominant status was associated with a significant shift in immunophenotypes towards favoring adaptive versus innate immunity. Using Tag-Seq to profile hepatic and splenic transcriptomes of alpha and subordinate males, we identified genes that regulate metabolic and immune defense pathways that are associated with status and/or CORT concentration. In the liver, dominant animals showed a relatively higher expression of specific genes involved in major urinary production and catabolic processes, whereas subordinate animals showed relatively higher expression of genes promoting biosynthetic processes, wound healing, and proinflammatory responses. In spleen, subordinate mice showed relatively higher expression of genes facilitating oxidative phosphorylation and DNA repair and CORT was negatively associated with genes involved in lymphocyte proliferation and activation. Together, our findings suggest that dominant and subordinate animals adaptively shift immune profiles and peripheral gene expression to match their contextual needs.

Purpose This study investigated the disclosure practices of people who stutter, and the relationship between disclosure of stuttering and quality of life. Method Participants were 322 adults who stutter recruited from speech-language pathologists and support group leaders. Participants completed a survey that contained items measuring level of disclosure of stuttering, as well as a global measure of self-rated quality of life. Participants were grouped into low, average, and high quality of life subgroups. Analysis of variance tests compared disclosure levels among these subgroups. Results The low quality of life subgroup reported significantly lower levels of disclosure compared to both the average and high quality of life subgroups. Participants with self-help/support group experience for stuttering demonstrated significantly higher levels of disclosure of stuttering compared to individuals without such experience. In addition, a substantial number of participants in the overall sample reported that they more than rarely feel the need to conceal stuttering from others (40%), and that no one knows that they stutter in many areas of life (37%). Conclusions Attempts to conceal stuttering in at least some life situations are not uncommon among adults who stutter. However, being involved in self-help support groups may be a helpful way of increasing disclosure of stuttering. Speech-language pathologists should become aware of the positive relationship between disclosure of stuttering and quality of life and its relevance in assessment and treatment when working with people who stutter.

This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population.Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL. Breath alcohol concentration was measured using the AlcoSense ™ Breathalyser on three separate visits. The primary end-point was the number of patients who were above the legal threshold for drink driving in Ireland.In total, 50 patients were recruited. 36 (68%) were female. The most common diagnosis was breast cancer (56%). Ten (20%) patients had metastatic disease and 4 (8%) had liver metastases. The mean paclitaxel dose administered was 118 mg. The mean amount of ethanol infused was 7.7 g. 27 patients had a detectable breath alcohol level on at least one visit. The mean breath alcohol concentration was 2 mcg/100 mL or 0.02 mg/L of breath. The maximum concentration of ethanol in exhaled breath was 11 mcg/100 mL or 0.11 mg/L which is 50% of the statutory limit for drink driving in Ireland. A weak correlation was observed between ethanol concentration in exhaled breath and the total amount of ethanol administered. Although no patient exceeded the general limit for drink driving in Ireland, three (6%) participants had a breath alcohol concentration above the threshold for professional, learner or novice drivers.Although definitive conclusions are limited by relatively small numbers, it seems unlikely that weekly paclitaxel infusions pose any significant risk to patients driving.

Purpose This study aimed to identify contributors to communicative participation in adults who stutter. Specifically, it was of interest to determine whether psychosocial variables of self-esteem, self-efficacy, and social support were predictive of communicative participation beyond contributions of demographic and speech-related variables. Method Adults who stutter ( N = 339) completed an online survey that included measures of communicative participation, self-esteem, self-efficacy, social support, self-reported speech-related variables (speech usage, number of years stuttering, history of treatment and self-help support group participation for stuttering, and physical speech disruption severity), and demographics (age, sex, living situation, education, and employment status). Hierarchical regression was performed for prediction of communicative participation, in addition to calculating Spearman correlations between social roles variables, communicative participation, and physical speech disruption severity. Results After controlling for demographic and speech-related variables, self-esteem, self-efficacy, and social support each significantly predicted communicative participation in adults who stutter. Large correlations were observed between communicative participation and measures of social roles, whereas medium correlations were observed between physical speech disruption severity and measures of social roles. Conclusions Communicative participation in adults who stutter is associated with a variety of demographic, speech-related, and psychosocial variables. Speech-language pathologists should be aware of predictors of communicative participation such as self-esteem, self-efficacy, and social support, in addition to severity of physical speech disruptions. They should consider and evaluate these factors in clients who stutter and target them in treatment if necessary.

Acetaminophen (also known as paracetamol) is a commonly used over-the-counter pain medication, but recent evidence suggests that a single exposure or prenatal exposure may have significant behavioral effects. This investigation aimed to determine whether acetaminophen could disrupt memory formation in an object-recognition task and to quantify potential changes in memory-related signaling cascades in the hippocampus of mice after acetaminophen administration. Using male mice, we examined the effect of a single subcutaneous injection of acetaminophen on the object-recognition task, a single-trial, hippocampus-dependent memory task. We also investigated potential changes in the activation of extracellular signal-regulated kinase (ERK) in the dorsal mouse hippocampus 1 hr after a subcutaneous injection of acetaminophen. We found that 50 mg/kg and 100 mg/kg interfered with performance in the object-recognition memory task, whereas 10 mg/kg did not. We also found that a single 50 mg/kg injection of acetaminophen significantly increased p42 ERK phosphorylation in the dorsal mouse hippocampus. Overall, these results suggest that a single dose of acetaminophen can have significant effects on memory and alters signaling kinases critical for memory consolidation. Further work is needed to determine the involved mechanisms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

BACKGROUND For Estrogen Receptor (ER) positive, early stage breast cancer, the 21 gene Recurrence Score (RS) has clinical use both as a prognostic tool and to predict chemotherapy benefit. The availability of this tool in Ireland has led to a reduction in the use of adjuvant chemotherapy for women with lymph node (LN) negative disease. However, the RS is not routinely funded for patients with LN positive (LN+) breast cancer in Ireland. In addition, there are limited international data on the use of this tool in the preoperative setting. In this prospective observational study, we are investigating whether access to the 21 gene RS leads to a reduction in the receipt of chemotherapy for patients with ER+, LN+ breast cancer, and to correlate the 21 gene RS with response to preoperative systemic therapy. TRIAL DESIGN This is a national, multi-site, prospective, observational study that will examine the impact of the 21 gene RS on chemotherapy recommendations in both the neoadjuvant and adjuvant setting. Prior to and following tumor testing with the 21 gene RS, Physicians will complete a questionnaire which details type and strength of systemic therapy recommendations. ELIGIBILITY Cohort 1 (postoperative) will include patients with ER+ tumors of any size with involvement of 1-3 lymph nodes (N1 including micrometastases). Cohort 2 (preoperative) will include patients with ER+, T2-T4 tumors with biopsy proven nodal metastases. Both cohorts will have ECOG PS 0 or 1 and be fit for consideration of chemotherapy as determined by the Investigator. SPECIFIC AIMS The primary endpoint is the percentage reduction in the number of patients for whom treating physicians recommend chemotherapy after testing with 21 gene RS. Secondary endpoints include the correlation between the 21 gene RS and residual cancer burden score, as well as pathological, clinical and radiological response rates. The economic impact of the 21 gene RS in ER+, LN+ will also be assessed. STATISTICAL METHODS The sample size is based on similar decision impact studies conducted in other countries. Physician recommendations for chemotherapy pre 21-gene RS and recommendations post 21-gene RS testing will be compared and percentage change estimated with 95% confidence intervals. For secondary endpoints, the Pearson correlation coefficient (rho) will be used to examine the strength of the correlation between the 21 gene RS category and response. A budget impact model will be used to estimate the cost reduction in adjuvant chemotherapy as a result of 21-gene RS testing. PRESENT ACCRUAL AND TARGET ACCRUAL Target accrual is 75 in each of the neoadjuvant and adjuvant cohorts to total 150 patients. Supported by Genomic Health. Citation Format: Keegan NM, Milewski M, Kelly CM, Murphy V, Chao C, Walsh J, Kennedy MJ, O'Connor M, Murphy C, O'Reilly S, Keane M, Duffy K, Hennessy B, Morris PG. The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor (ER) positive, lymph node positive early stage breast cancer in Ireland [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-04-03.

Simultaneous measurements of the lightning return-stroke current derivative at the Canadian National (CN) Tower and the corresponding lightning electromagnetic pulse (LEMP) 2 km north of the tower have been performed since 1991 using broadband, high-resolution measurement systems. The recent installation of global positioning systems for time synchronization of CN Tower lightning measurement stations has enabled the correlation of the wavefront characteristics (peak, maximum derivative, and 10-90% rise time) of the return-stroke current with those of its LEMP. The characteristics of the tower's lightning electric and magnetic fields have also been correlated with each other. The current and field correlation analysis is based on August 19, 2005, CN Tower lightning return-stroke data. In addition to the strong linear correlations of the wavefront characteristics of the electric and magnetic field waveforms, an excellent linear correlation has been established between the magnetic field and current wavefront peaks. Also, a good linear correlation has been found between the magnetic field wavefront maximum derivative and that of the current. These findings are of interest in lightning detection methodology. For example, the current wavefront maximum derivative can be estimated from the detected magnetic field after taking into consideration the propagation effect on its derivative. Although weakly correlated, a general trend of increase in the magnetic field peak and maximum rate of rise has been observed as the current maximum rate of rise and peak increase, respectively. It is hoped that the field-current relationships developed in this paper, using the recent CN Tower lightning return-stroke data, will contribute to solving the inverse-source problem, one of the challenging problems in lightning research, where lightning current characteristics are estimated based on the characteristics of the measured LEMP.

DYT1 primary torsion dystonia is an autosomal dominant disorder caused by deletion of a GAG triplet in exon 5 of the DYT1 gene. A significant proportion of individuals with early-onset generalized dystonia is believed to be DYT1 mutation carriers. We assessed the frequency of the GAG deletion in the DYT1 gene in a group of 61 Polish probands with clinical diagnosis of primary dystonia. The deletion was identified in four probands presenting with early-onset generalized disease (7%). Further studies in probands' families revealed two symptomatic and nine asymptomatic mutation carriers. We tested all mutation-positive individuals for the presence of some common polymorphisms within the DYT1 gene. Two of the 15 mutation-positive individuals additionally carried polymorphisms in 3'-UTR of the gene. Early onset in a limb and progression toward a generalized form, but not family history of dystonia, are indicative of DYT1 dystonia in Polish dystonic individuals.

It has been observed that tall structures are sometimes struck by lightning below their tops. This phenomenon necessitates the use of special procedures for the protection of tall structures from lightning hazards. This paper focuses on the analysis of lightning flashes that struck the CN Tower below its tip over an extended period of time (1991–2005). Through the use of video images recorded during the reporting period, it was found that out of 404 flashes to the tower, only 16 hit the tower below its tip (3.96%). The distance between the tower's tip and the strike location varied from 5.4 to 70 m. Statistical analysis of flash characteristics of strikes below the tower's tip generally shows that the flash duration and the number of strokes per flash are considerably lower than those for the majority of cases, when the tower is struck at its tip. Furthermore, a trend of decrease in flash duration is found as the distance between the tower's tip and the strike location increases. Therefore, based on the analysis of the available data, lightning strikes below the top of a tall structure do not seem to pose greater danger than strikes to the structure's top, assuming that the structure is also protected along its sides. It is hoped that the presented observations and statistical analyses will be of value in the development of sophisticated measures against lightning hazards at elevated objects.

This paper presents the results of hydrofoil simulations at varying depths below the free surface, in surface piercing conditions, and integrated with ship hulls. It focuses on the influence of the free surface on the hydrodynamic loads, susceptibility to cavitation, and resulting surface wave patterns. A fast, high-order, NURBS (Non Uniform Rational B-Spline) based boundary element method has been developed that includes both free surface boundary conditions and steady and unsteady iterative pressure Kutta conditions for simulating lift. Results from this method will be compared to published experimental results, analytical solutions based on linear potential theory, and numerical results from viscous simulations obtained using the commercial CFD solver, ANSYS CFX.

The reduced order model at the heart of the APS Environmental and Ship Motion Forecasting system must retain the accuracy of a higher fidelity seakeeping code while simultaneously meeting computational speed required to provide motion forecasts minutes into the future for two or more ships operating in close proximity. We describe the mathematical formulation of the reduced order model and efficient modeling techniques to construct databases of wave force Response Amplitude Operators and Impulse Response Functions before presenting comparisons between the reduced order model, a higher fidelity seakeeping code called AEGIR, and experimental data for the R/V Melville and two multi-ship configurations.

Objectives: This article discusses the toxicity of the most common poisonous plants known to cause life-threatening systemic effects or death in dogs and cats as reported to the ASPCA Animal Poison Control Center (APCC). Data sources: The article presents an overview of geographic distribution, toxic principle, clinical signs, clinical chemistry alterations, and treatment of intoxication as reported in the literature and based upon data retrieved from the APCC between January 2001 and December 2003. Summary: Most plant exposures in dogs or cats result in mild to moderate signs of vomiting and diarrhea while liver, kidney, central nervous system, or cardiovascular effects are rare. Some garden or household plants can cause serious systemic effects or death when a small amount of plant material has been ingested. Based on APCC records, the most frequently reported poisonous plants causing serious systemic effects include Lily (Lilium and Hemerocallis spp.), Azalea (Rhododendron spp.), Oleander (Nerium oleander), Sago palm (Cycas spp.), Castor bean (Ricinus communis), Kalanchoe (Kalanchoe spp.), and Autumn Crocus (Colchicum autumnale). Conclusion: Despite the variety of toxins present in the plants listed above, early clinical signs of toxicosis in dogs and cats can be nonspecific and can include vomiting, lethargy, anorexia, salivation, or diarrhea. Cardiac arrhythmias may be present with oleander, azalea, or kalanchoe ingestion. Evidence of liver or kidney damage (Cycas, Lilium, Hemerocallis spp., Ricinus communis) may occur 1–2 days after the exposure. Treatment consists of early decontamination and supportive care and may vary according to the type of plant involved and clinical signs present.

Lightning strikes to the Toronto Canadian National (CN) Tower have been observed since 1978. In this paper, a brief description of the lightning measurement systems is provided, with emphasis on the current measurement system. Current and field measurement systems with broad bandwidths and high resolutions have been operational since 1991. Typical current derivative and current waveforms of a CN Tower lightning return stroke are also presented. Extensive cumulative statistics of waveform parameters (maximum steepness, risetime to maximum steepness, wavefront peak, risetime to wavefront peak, and absolute peak) of lightning return-stroke current signals measured at the CN Tower during a 10-year period have been derived. The statistical analysis shows that in 50% of the current records: the current wavefront maximum steepness exceeds 18.8 kA/μs, the risetime to maximum steepness exceeds 138 ns, the current wavefront peak exceeds 5 kA, the risetime to wavefront peak exceeds 636 ns and the current absolute peak exceeds 7.2 kA. The statistical analysis also shows that first return strokes feature lower current steepness and higher current peak when compared with subsequent return strokes. Recommendations concerning instrumentation and techniques for the proper measurement of lightning return-stroke currents are discussed. The presented statistical results will be of assistance in the establishment of more sophisticated protective measures against lightning hazards, especially at elevated objects.

Zebra finches communicate via several distinct vocalizations, of which song is the most studied. Behavioral observations indicate that adults are able to discriminate among the songs of different conspecific individuals. In the wild, zebra finches live in structured but mobile colonies, and encounter new individuals on a frequent basis. Thus it seems plausible that adult finches might have the capacity to recognize and remember new songs they encounter on a single day, but this has never been directly tested. Here we devised a simple observational assay to determine whether adult male zebra finches show recognition of a song they have heard repeatedly from taped playbacks, over a single three hour period the day before. We quantified the rate of production of six discrete behaviors (short calls, contact calls, singing, short hops, long hops, and beak swipes) made by adult male zebra finches as they listened to the playbacks. At the onset of song playback, all birds suspended these behaviors and sat silently-occasionally moving their heads. Then, after a measurable period ("response latency"), the birds resumed these activities. We observed that the response latency was long (approximately 10 min) when birds were hearing a particular song for the first time. The response latency was much shorter (approximately 1-2 min) when the birds had heard the same song the day before. Thus, functional song memories must result from as little as 3 h of passive song-exposure. These results suggest that ongoing song learning may play a natural role in the daily life of adult zebra finches, and provide a behavioral reference point for studies of molecular and physiological plasticity in the adult auditory system.

Insulin-like growth factor I (IGF-I) is required for normal embryonic development and postnatal growth. Like most hormones and growth factors, IGF-I is synthesized as a proprotein that is converted to the mature form by endoproteolysis. Processing of pro-IGF-I to mature IGF-I occurs by cleavage within the unique pentabasic processing motif Lys-X-X-Lys-X-X-Arg71-X-X-Arg-X-X-Arg77. We have previously shown that human embryonic kidney 293 cells process pro-IGF-IA at Arg71 to generate IGF-I-(1-70) and at Arg77 to produce IGF-I-(1-76). Cleavage at each of these sites requires upstream basic residues, indicating that subtilisin-related proprotein convertases (SPCs) may be involved. In order to investigate the identity of the endogenous enzymes involved in maturation of pro-IGF-IA, we have expressed wild-type and mutant pro-IGF-IA in 293 cells and in the furin-deficient Chinese hamster ovary cell line, RPE.40. We have also co-expressed these constructs with SPCs that are thought to play a role in processing precursor proteins in the constitutive pathway: furin, PACE4, PC6A, PC6B, and LPC. The results show that furin is most active at cleaving wild-type and mutant pro-IGF-IA and can cleave these precursors at multiple sites within the pentabasic motif. PC6A and LPC are less active than furin but cleave only at Arg71. PACE4 and PC6B have very little activity on pro-IGF-IA precursors. Wild-type pro-IGF-IA was correctly processed to mature IGF-I in 10 of 10 cell lines that were tested. Since furin, PC6A, and LPC are known to have a broad pattern of tissue distribution and we have demonstrated expression of LPC in RPE.40 cells, our results suggest that these SPCs may be responsible for the endogenous pro-IGF-IA processing activity observed in a wide variety of cell lines.

We previously reported the isolation of a laboratory-derived Staphylococcus aureus mutant, 523k, that has constitutive low-level resistance to vancomycin (MIC = 5 micrograms/ml) and teicoplanin (MIC = 5 micrograms/ml) and elaborates a ca. 39-kDa cytoplasmic protein that was not detected in the parent strain 523 (MIC = 1 micrograms/ml). We have now detected the protein in strain 523 by immunoblotting with antiserum raised against the protein. Consistent with our initial observations, densitometric analysis of the immunoblots revealed an increased production of the protein in 523k compared with that of the susceptible parent 523. The 5' region of the gene encoding the protein of interest was identified by nucleotide sequencing a PCR product amplified from the genome of 523k with degenerate primers designed to encode the amino acid sequence of proteolytic peptides obtained from the protein. The remainder of the gene was identified by library screening, PCR, and nucleotide sequencing. The gene encodes a 36.7-kDa protein with homology to a family of bacterial NAD+-dependent, D-specific 2-hydroxyacid dehydrogenases which includes both D-lactate dehydrogenase and the enterococcal vancomycin resistance protein VanH and is therefore designated ddh. Increased production of the product of ddh, Ddh, was associated with increased D-lactate dehydrogenase activity in 523k, a finding which suggested that Ddh is likely to be the D-lactate dehydrogenase previously identified in S. aureus. The increased D-lactate dehydrogenase activity in strain 523k and the structural similarities among Ddh, D-lactate dehydrogenase, and VanH suggest that overproduction of Ddh might play a role in vancomycin resistance in this strain.

Background: The combination of the anthracycline, doxorubicin with cyclophosphamide (AC) is a widely used chemotherapy regimen in early stage breast cancer. Studies have shown that dose dense chemotherapy (incorporating AC) improved both disease-free survival and overall survival compared to once every 3 week treatment with daily subcutaneous G-CSF support. An important advance in the use of dose dense chemotherapy regimens was the development of pegylated forms of G-CSF, which offered the convenience of a single subcutaneous injection, rather than multiple daily injections. Lipegfilgrastim is a pegylated long-acting covalent conjugate of filgrastim (G-CSF). In a pivotal randomised phase III study in breast cancer lipegfilgrastim was shown to be non-inferior to pegfilgrastim. Although lipegfilgrastim is licensed in Europe and can facilitate every 2 week (dose dense) scheduling of chemotherapy there are a lack of prospective data about its efficacy in this setting. In this prospective, non-interventional, study we are investigating the incidence of treatment-related neutropaenia following four cycles of dose dense AC with lipegfilgrastim support. Methods: The primary end point of this prospective, single arm study is to determine the incidence of treatment-related neutropaenia, defined as an absolute neutrophil count (ANC) of 38°C and ANC Citation Format: Lyons T, Mallet V, Collins D, Malone E, Milewski M, Egan K, Hennessy B, Grogan L, Breathnach O, Morris P. An observational study of dose dense chemotherapy with lipegfilgrastim support in early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-03.

This electronic document is a "live" template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document. The maximum number of pages allowed for each paper is six, including figures, tables and references.

Summary We have determined IgG subclass concentrations in 100 patients with aspirin-induced asthma and 80 healthy controls. Patients on chronic corticotherapy (n= 64) had significantly lower total IgG levels than patients not receiving steroids (n= 36) or controls. Corticotherapy was not associated with changes in the subclass distributions. In patients, the most striking finding was elevation of IgG4. It was not related to corticotherapy or serum IgE levels. The rise in IgG4 was accompanied by a modest, though statistically significant, depression of IgG1. No changes of IgG2 and IgG3 concentrations were observed. Thus, aspirin-induced asthma is characterized by a distinct pattern of distributions of IgG subclasses. It is suggested that in aspirin-induced asthma elevation of IgG4 might result from chronic antigenic stimulation, of viral origin, and that determination of IgG subclass distribution might be of clinical interest.

The lightning discharge has been studied by many researchers for over a century. One of the most important parameters that is of interest to researchers (especially from the point of view of protection) is the lightning return-stroke current. In order to directly measure the lightning current one must know the exact location of lightning strikes, which can only be accomplished using instrumented tall towers, towers placed on elevated grounds or by rocket-triggered lighting experiments. In most investigations, the lightning current characteristics are determined from measured electric and magnetic fields through the usage of a lightning return-stroke model. In this paper, a lightning return-stroke transmission line (TL) model, based on the measured lightning return-stroke current derivative at the CN Tower is presented. Using the TL model along with the derivative of Heidler function, the paper focuses on the determination of the lightning current special temporal distribution along the current path during the lightning return-stroke phase. Current reflections resulting from the four main CN Towerpsilas structural discontinuities have been thoroughly studied and their proper values are determined and used in modeling of the current distribution along the CN Tower.

Expanding demand on the Internet services leads to an increased role of the network dimensioning problem for elastic traffic where one needs to allocate bandwidth to maximize service flows and simultaneously to reach a fair treatment of all the elastic services. Thus, both the overall efficiency (throughput) and the fairness (equity) among various services are important. The max-min fairness (MMF) approach, widely used to this problem, guarantees fairness but may lead to significant losses in the overall throughput of the network. In this paper we show how the concepts of multiple criteria equitable optimization can be effectively used to generate various fair resource allocation schemes. We introduce a multiple target model equivalent to equitable optimization and we develop a corresponding procedure to generate fair efficient bandwidth allocations. The procedure is tested on a sample network dimensioning problem and its abilities to model various preferences are demonstrated.

Since 1991, broadband, high-resolution measurement systems have simultaneously captured the lightning current derivative at the CN tower and the corresponding lightning-generated electric and magnetic fields 2 km north of the tower. Extensive cumulative statistics of waveform parameters (peak, 10% to 90% risetime to peak and pulse width at the 50% level of the peak) of electric and magnetic field signals, generated by lightning return-strokes to the CN Tower during the past eleven years (1992-2002), have been derived and are presented in this paper. Furthermore, waveform parameters of electric fields radiated from lightning strikes to the CN Tower and to other objects in its vicinity are compared. It is shown that the risk from electromagnetic interference (EMI) due to the lightning-generated electromagnetic pulse (LEMP) is substantially elevated near a tall structure. The presented statistical results will assist in the establishment of more sophisticated protective measures against interference due to lightning-generated electromagnetic pulses, especially those generated from lightning occurring at tall structures.

Lightning strikes to the Toronto CN Tower have been monitored since 1978. In this paper, a detailed description of the current measuring system installed at the Tower in 1990 and extended in 1997 is given. Typical current derivative and current waveforms of CN Tower strikes are presented. Cumulative statistics of the wavefront characteristics of lightning currents (maximum steepness, wavefront peak and risetime) measured at the CN Tower in 1999 are derived. These statistics have led to recommendations concerning instrumentation and techniques for the proper measurement of lightning currents especially for those encountered at elevated objects.

Spontaneous emphysema is not only the rate complication of bronchial asthma but may also be the first, atypical manifestation of the disease. We have presented here the case report of a young man in whom the occurrence of spontaneous pneumomediastinum with subcutaneous emphysema and pneumothorax led to the diagnosis of bronchial asthma.

Polarization of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel to the apical plasma membrane in epithelial cells is critical for vectorial chloride transport. Previously, we reported that the C terminus of CFTR constitutes a PDZ-interacting domain that is required for CFTR polarization to the apical plasma membrane and interaction with the PDZ domain-containing protein EBP50 (NHERF). PDZ-interacting domains are typically composed of the C-terminal three to five amino acids, which in CFTR are QDTRL. Our goal was to identify the key amino acid(s) in the PDZ-interacting domain of CFTR with regard to its apical polarization, interaction with EBP50, and ability to mediate transepithelial chloride secretion. Point substitution of the C-terminal leucine (Leu at position 0) with alanine abrogated apical polarization of CFTR, interaction between CFTR and EBP50, efficient expression of CFTR in the apical membrane, and chloride secretion. Point substitution of the threonine (Thr at position -2) with alanine or valine had no effect on the apical polarization of CFTR, but reduced interaction between CFTR and EBP50, efficient expression of CFTR in the apical membrane as well as chloride secretion. By contrast, individual point substitution of the other C-terminal amino acids (Gln at position -4, Asp at position -3 and Arg at position -1) with alanine had no effect on measured parameters. We conclude that the PDZ-interacting domain, in particular the leucine (position 0) and threonine (position -2) residues, are required for the efficient, polarized expression of CFTR in the apical plasma membrane, interaction of CFTR with EBP50, and for the ability of CFTR to mediate chloride secretion. Mutations that delete the C terminus of CFTR may cause cystic fibrosis because CFTR is not polarized, complexed with EBP50, or efficiently expressed in the apical membrane of epithelial cells.

This paper describes new calculations of broadband stator noise from the ingestion of rapidly distorting turbulence. The stator blades may be thick, cambered, and at an arbitrary angle of attack relative to upstream infinity. The new numerical tool applies Notre Dame’s Euler code “CASGUST” to compute the basic influence function for gust ingestion by a cascade in freefield. i.e., in the absence of a finite-length diffraction duct, or cowl. The theory accounts fror spanwise variations in the building-block input gusts, on the resulting blade loading patterns, and so also on the computed nearfield and farfield pressures, the predictions of broadband radiated stator noise address observer positions both in the aircraft and ground reference frames. They are in the form of frequency spectra for any prescribed ray direction, and of directivity patterns for any chosen frequency.

Development of the mammalian pancreas has been studied extensively in mice. The stages from budding of the pancreatic anlaga through endocrine and exocrine cell differentiation and islet formation have been described in detail. Recently, the homeodomain transcription factor PDX-1 has been identified as an important factor in the proliferation and differentiation of the pancreatic buds to form a mature pancreas. To evaluate the possibility of using zebrafish as a model for the genetic analysis of pancreas development, we have cloned and characterized PDX-1 from this organism. The deduced sequence of zebrafish PDX-1 contains 246 amino acids and is 95% identical to mammalian PDX-1 in the homeodomain. We also cloned zebrafish preproinsulin complementary DNA as a marker for islet tissue. By in situ hybridization we demonstrate that PDX-1 and insulin are coexpressed during embryonic development and in adults, although PDX-1 expression appears to be biphasic. Insulin expression apparently begins before 44 hpf, the earliest stage examined in this study. Additionally, very high levels of PDX-1 expression were observed in the pyloric caeca, the accessory digestive organs that also are derived from the proximal region of the intestine in teleosts. Finally, our data show that the evolutionary conservation of zebrafish PDX-1 extends to its DNA binding properties. Zebrafish PDX-1 was equally as effective as mouse PDX-1 in stimulating insulin gene transcription, and maximum promoter activation was dependent on the presence of four intact A elements. The demonstration of this capability suggests that transcriptional regulatory mechanisms that control pancreatic development and insulin gene expression have been conserved among vertebrates.

We performed a double-blind, crossover, placebo-controlled study on the effect of fluticasone propionate (FP) treatment on chronic eosinophilic rhinosinusitis in 15 patients with aspirin-induced asthma (AIA). There were 10 women and five men aged 32-60 years; average: 45 years. After a 10-day run-in period, patients underwent two 4-week treatment courses (FP vs placebo), separated by a 2-week washout interval. Clinical activity of FP was evaluated by daily measurement of peak nasal inspiratory flow (PNIF) and a scoring system of subjective symptoms. Nasal challenges with E-lysine aspirin, using active anterior rhinomanometry, were performed at the entry and on the last day of each treatment period. Weekly mean values of symptom scores were generally lower and PNIF measurements higher during treatment with FP than with placebo. This difference was statistically significant for most recorded parameters for the whole 4-week FP treatment. On average, the reactions evoked by aspirin nasal challenge were significantly shorter and milder after treatment with FP than with placebo. In 8/13 patients, FP completely prevented aspirin-precipitated nasal reaction, whereas protection after placebo was observed in only 2/12 subjects (P = 0.004). We conclude that intranasal FP is an effective therapy for chronic eosinophilic rhinitis in patients with AIA.

Background Conventional risk factors of coronary artery disease fail to explain accelerated atherosclerosis in systemic lupus erythematosus (SLE) patients. Clinical and experimental studies shows that soluble intercellular adhesion molecule 1 (sICAM-1) and von Willebrand factor (vWF) levels reflect endothelial damage or dysfunction. Objectives This study was conducted to determine the possible influence of endothelial pathology assessed by sICAM-1 and vWF levels on coronary artery calcifications in SLE patients. Methods In 60 SLE patients in stable clinical conditions, without a prior history of coronary artery disease, MultiDetector Computed Tomography (MDCT)-based coronary calcium scoring was performed. Laboratory evaluation included serum concentrations of sICAM-1, vWF, C-reactive protein (CRP) and antinuclear antibodies (ANA) titers. Results MDCT revealed coronary calcifications in 15 (25%) patients. Calcium scores ranged from 0.3 to 843.2 (median 31,7). No association was found between these scores and conventional coronary artery disease risk factors (obesity, hypertension, tobacco use, hyperlipidaemia, diabetes) nor CRP levels. On the contrary, as compared to patients with calcium score =0, in those with coronary calcifications higher concentrations of sICAM-1 (382.2±328.2 vs. 267.1±62.7, p=0.01), vWF (188.5±87.6 vs. 149.2±52.2, p=0.025) and higher ANA titers (8320±4521 vs. 4668±2717, p=0.03) were found. Conclusions Conventional risk factors of coronary artery disease as well as markers of an ongoing inflammation do not show significant association with coronary artery calcifications in SLE patients. Calcified atherosclerotic plaques were observed mainly in patients with elevated levels of sICAM-1, vWF or high ANA titers. The sICAM-1 and vWF levels may serve as a possible risk marker of coronary calcifications and may have a prognostic importance. Disclosure of Interest None Declared

This study aimed to evaluate the immune system function in patients with uveitis of unknown aetiology.The clinical material comprised 19 patients with endogenous uveitis. In all cases the following immunological tests were performed: serum immunoglobulins A, G, M, total IgE, circulating immune complexes, complement components C3c and C4-all determined by laser nephelometry; antinuclear antibodies assessed with indirect immunofluorescence method using HEp-2 cell lines; and antineutrophil cytoplasmic antibodies using indirect immunofluorescence test. In 4 cases lupus anticoagulant was measured with APTT and dRVVT assays.Among our 19 examined patients immunological abnormalities were found in 12 cases. Changes in immunoglobulin concentrations were found in 8 cases. In 4 patients abnormalities of the complement system were observed. Antinuclear antibodies with speckled pattern in indirect immunofluorescence were present in 7 cases.In a proportion of patients with endogenous uveitis mild immunological abnormalities were present, suggesting an autoimmune background of the disease. Studies of the immunological profile can therefore help in better evaluation of the patients. It remains to be determined whether the observed immunological alterations are of any importance in the pathogenesis of the studied disease.

Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by various immunologic abnormalities. We have studied the efficacy of recombinant human interferon gamma (rhINF-gamma) administered subcutaneously at a dose of 0.05 mg/m2 in ten patients with severe AD. Patients were treated for 4 weeks. They have shown marked clinical improvement starting from the third week of treatment. The efficacy of the drug varied, with erythema, dryness and lichenification being the most responsive symptoms. There was no change in serum immunoglobulin E and IgG4 levels. Whole blood eosinophil count decreased only transiently and was accompanied by a tendency to lower values of serum eosinophil cationic protein. Patient with AD showed an increased expression of a T-cell surface activation marker CD 25 as compared to healthy controls. Moreover, clinical improvement was roughly paralleled by the decrease in this T-cell activation marker. We conclude that rhINF-gamma is a novel efficacious therapeutic approach in severe AD. We suggest that its primary action might be related to the inhibition of T-cell activation.

A vortex lattice method lifting surface code and an axisymmetric incompressible Navier-Stokes (RANS) code have been interactively coupled to design wake-adapted propellers. A new body force model has been implemented to represent the axisymmetric component of the flow consistently in both models.

"Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of vancomycin and teicoplanin, respectively, were selected from 2 susceptible clinical isolates of Staphylococcus aureus by serial incubation in low-level vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic fraction and occasionally in the membrane fraction by SDS-PAGE of both derivatives. This protein was purified by DEAE chromatography, preparative SDS-PAGE, and electroelution. Derivative bacteria were larger on transmission electron microscopy, had thicker cell walls, and had changes in colony morphology on solid media. Further evidence for cell wall reorganization included loss of phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme killing, and changes in condition for detection of optimal coagulase activity. The mechanism of decreased susceptibility to glycopeptide antibiotics among S. aureus derivative isolates is uncertain. The production of the approximately 39-kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its cell wall target.

Serum lipoprotein(a) concentration in men with hypertension, arteriosclerosis obliterans, hypercholesterolemia and after myocardial infarction was measured using Laurell's immunoelectrophoresis. Lp(a) distribution and mean serum concentrations did not differ significantly from the controls, with the exception of a group of premature myocardial infarction (age below 45), in which high values were more frequent.