Increasing dietary levels of the n-3 long-chain PUFA, EPA and DHA, improves the growth, welfare, robustness and fillet quality of Atlantic salmon in sea cages.

The present study evaluated the effects of increasing the dietary levels of EPA and DHA in Atlantic salmon (Salmo salar) reared in sea cages, in terms of growth performance, welfare, robustness and overall quality. Fish with an average starting weight of 275 g were fed one of four different diets containing 10, 13, 16 and 35 g/kg of EPA and DHA (designated as 1·0, 1·3, 1·6 and 3·5 % EPA and DHA) until they reached approximately 5 kg. The 3·5 % EPA and DHA diet showed a significantly beneficial effect on growth performance and fillet quality compared with all other diets, particularly the 1 % EPA and DHA diet. Fish fed the diet containing 3·5 % EPA and DHA showed 400-600 g higher final weights, improved internal organ health scores and external welfare indicators, better fillet quality in terms of higher visual colour score and lower occurrence of dark spots and higher EPA and DHA content in tissues at the end of the feeding trial. Moreover, fish fed the 3·5 % EPA and DHA diet showed lower mortality during a naturally occurring cardiomyopathy syndrome outbreak, although this did not reach statistical significance. Altogether, our findings emphasise the importance of dietary EPA and DHA to maintain good growth, robustness, welfare and fillet quality of Atlantic salmon reared in sea cages.

Dietary inclusion of Antarctic krill meal during the finishing feed period improves health and fillet quality of Atlantic salmon (Salmo salar L.).

There is an urgent need to find alternative feed resources that can further substitute fishmeal in Atlantic salmon diets without compromising health and food quality, in particular during the finishing feeding period when the feed demand is highest and flesh quality effects are most significant. This study investigates efficacy of substituting a isoprotein (35 %) and isolipid (35 %) low fishmeal diet (FM, 15 %) with Antarctic krill meal (KM, 12 %) during 3 months with growing finishing 2·3 kg salmon (quadruplicate sea cages/diet). Final body weight (3·9 (se 0·04) kg) was similar in the dietary groups, but the KM group had more voluminous body shape, leaner hearts and improved fillet integrity, firmness and colour. Ectopic epithelial cells and focal Ca deposits in intestine were only detected in the FM group. Transcriptome profiling by microarray of livers showed dietary effects on several immune genes, and a panel of structural genes were up-regulated in the KM group, including cadherin and connexin. Up-regulation of genes encoding myosin heavy chain proteins was the main finding in skeletal muscle. Morphology examination by scanning electron microscopy and secondary structure by Fourier transform IR spectroscopy revealed more ordered and stable collagen architecture of the KM group. NEFA composition of skeletal muscle indicated altered metabolism of n-3, n-6 and SFA of the KM group. The results demonstrated that improved health and meat quality in Atlantic salmon fed krill meal were associated with up-regulation of immune genes, proteins defining muscle properties and genes involved in cell contacts and adhesion, altered fatty acid metabolism and fat deposition, and improved gut health and collagen structure.

Efficacy and safety of ingenol mebutate gel in field treatment of actinic keratosis on full face, balding scalp, or approximately 250 cm2 on the chest: A phase 3 randomized controlled trial.

BACKGROUND: Ingenol mebutate (IngMeb) 0.015% or 0.05% is approved for actinic keratosis (AK) areas of 25 cm2 or less; some patients require treatment of larger fields. OBJECTIVE: To determine efficacy and safety of IngMeb 0.027% in areas of AK of up to 250 cm2 during an 8-week initial assessment period and extended 12-month follow-up. METHODS: This phase 3, randomized, double-blind, vehicle-controlled trial (NCT02361216) enrolled adult patients with 5 to 20 AK lesions on the face/scalp (25-250 cm2) or chest (approximately 250 cm2). Patients received once-daily IngMeb or vehicle for 3 consecutive days on the full face, full balding scalp, or approximately 250 cm2 on the chest. The primary endpoint was complete AK clearance (AKCLEAR 100; week 8). Additional endpoints included partial AK clearance (AKCLEAR 75), recurrence, patient satisfaction, cosmetic outcome, and safety. RESULTS: IngMeb was superior to vehicle for complete AK clearance (21.4% vs 3.4%, P < .001) and AK clearance of 75% or greater (59.4% vs 8.9%, P < .001) at week 8. Probability of sustained clearance during the 12-month follow-up was 22.9% for patients treated with IngMeb. Increased treatment satisfaction and cosmetic outcomes were observed with IngMeb versus vehicle. No unexpected safety signals were identified. LIMITATIONS: Localized skin responses hindered maintenance of double-blinding. CONCLUSIONS: IngMeb 0.027% was superior to vehicle for treatment of AK areas of up to 250 cm2. The safety profile of IngMeb was as expected.

Real-World Effectiveness and Safety of Field- and Lesion-Directed Treatments for Actinic Keratosis.

Background: Real-world data for actinic keratosis treatment in the United States is lacking. Objectives: To understand real-world treatment patterns for actinic keratosis by type and modality, and compare effectiveness and safety of therapies, either alone or in combination. Methods: Medical charts of 429 patients were identified; clinical and outcome data were analyzed. Results: The first treatment after the index diagnosis was most frequently a procedure, followed by a topical agent. Treatment with 5-fluorouracil, ingenol mebutate, imiquimod, cryotherapy, or cryotherapy plus one topical (CRYO+One Topical) reduced actinic keratoses by 66.0%, 69.3%, 72.5%, 72.9%, and 73.0%, respectively; ≥75% clearance (AKCLEAR 75) was achieved in 57.1%, 72.7%, 57.1%, 62.4%, and 62.0% of those patients. Treatment effectiveness was positively correlated with the number of baseline actinic keratoses for topical and for procedural plus topical combination treatments, but not for procedural treatments alone. Adverse reactions (ARs) were more common with cryotherapy (9.7%); local skin responses (LSRs) were more common with field-directed (18.5%-43.1%) and CRYO+One Topical therapy (21.3%). Limitations: This was a retrospective study of limited duration and population size. Conclusions: The most commonly used treatments for patients with 6 or more actinic keratoses were topicals and a procedure plus topical combination, which also achieved higher rates of complete clearance than a procedure alone. ARs and LSRs were few in frequency and type.

Efficacy and safety of ingenol disoxate gel in field treatment of actinic keratosis on full face, scalp or large area (250 cm2) on the chest: results of four phase 3 randomized controlled trials.

INTRODUCTION: Actinic keratosis (AK) is a skin condition arising from chronic exposure to ultraviolet light and may lead to the development of malignancies. This trial aimed to evaluate efficacy and safety of ingenol disoxate gel (IngDsx, 0.018% for face/chest [FC]; 0.037% for scalp [S]), versus vehicle. METHODS: Four identical phase 3 trials in patients with AK on the full face/up to 250cm2 of chest or full balding scalp, with an initial 8-week period and 12-month follow-up, were conducted. FC and S trials were pooled for analysis. The primary endpoint was complete clearance at Week 8. RESULTS: Across trials, 616 patients were randomized to FC and 626 to S, with 410 and 420 assigned to receive IngDsx, respectively. In the FC and S trials, 25.9% and 24.5% of patients in the IngDsx group, respectively, achieved the primary endpoint. IngDsx was relatively well tolerated. During extended follow-up, there were more identified non-melanoma skin malignancies in the IngDsx group than vehicle group; HR: 2.38 (95% CI: 1.28, 4.41). CONCLUSION: Treatment with IngDsx was superior to vehicle on all clinical endpoints, patient-reported and cosmetic outcomes. During the 12-month follow-up, slightly increased skin malignancies in the treatment area were identified, potentially due to unintentional detection bias.

Curious, thoughtful and affirmative-Young children's meanings of participation in healthcare situations when using an interactive communication tool.

AIMS AND OBJECTIVES: To describe young children's demonstrated participation in healthcare situations while using an interactive communication tool. BACKGROUND: Participation is a multidimensional concept influenced by situational and contextual issues. In child participation, verbal and nonverbal communicative expressions are of interest, as both demonstrate the child's perspective. Children have a right to participate in all situations that matter to them, for instance healthcare situations. Children, understood as social actors, express a wish and a need to participate in these situations to get information and to enable preparation. DESIGN/METHOD: In a pilot study, video observations were used to capture the children's use of the interactive communication tool in healthcare situations. A hermeneutic analysis was conducted to achieve a deeper understanding of the children's demonstrated cues of participation. RESULTS: The expressed cues of participation were understood as having either a curious, thoughtful or affirmative meaning of participation and there was a continuous movement between them. Curious cues were expressed when introducing or reintroducing the tool in the situation and demonstrated a wish to get knowledge of the things shown on the screen or to perform the virtual tasks. Thoughtful cues slowed down the progression of the situation when the children needed time to think or adapt to the virtual procedures. Affirmative cues were self-rewarding and demonstrated at successful task performance. CONCLUSION: An interactive communication tool used in healthcare situations can promote young children's understanding and facilitate their situated participation, which potentially reduces feelings of distress or anxiety. This innovative use of interactive technology within paediatric health care provides new ways of revealing the child's perspective in the situation. RELEVANCE TO CLINICAL PRACTICE: Interactive technology improves understanding and participation of children in healthcare situations, which impact them positively, both in the present and for the future. A communication tool enhances professionals' opportunities to adopt a child-centred approach by responding sensitively to the children's expressions.

Gene expression profiling in melanised sites of Atlantic salmon fillets.

Black spots, which deteriorate quality of Atlantic salmon fillets represent a significant problem for commercial aquaculture. These areas are characterized with accumulation of melanomacrophages, occasional formation of granulomas and substitution of skeletal muscle with connective tissue. A number of possible causative agents have been suggested including vaccination and infection with piscine reovirus (PRV). We report transcriptome profiling of melanised foci with oligonucleotide DNA microarrays. Analyses revealed a multitude of differentially expressed genes associated with melanogenesis, metabolic changes and formation of scar. The immune profile was characterized with inflammation, preferential activation of classical complement pathway, MHCII and helper T cells combined with strong B cells responses and massive induction of immunoglobulins; innate antiviral responses were relatively weak in sharp contrast to PRV-caused heart and skeletal muscle inflammation and other viral infections. A panel of immune genes with specific activation in dark spots was found, most up-regulated were CD209-like lectin (44-fold) and prostaglandin reductase (11-fold). Further, RNA sequencing was performed on the same material to search for the presence of putative pathogens. Transcripts of prokaryotic rRNA with exclusive or preferential location in black spots were found. Results suggest mild chronic inflammation initiated with trauma, bacterial or viral infection followed by sustained immune responses to opportunistic microorganisms as a realistic scenario of dark spots formation.

The child's perspective as a guiding principle: Young children as co-designers in the design of an interactive application meant to facilitate participation in healthcare situations.

During the last decade, interactive technology has entered mainstream society. Its many users also include children, even the youngest ones, who use the technology in different situations for both fun and learning. When designing technology for children, it is crucial to involve children in the process in order to arrive at an age-appropriate end product. In this study we describe the specific iterative process by which an interactive application was developed. This application is intended to facilitate young children's, three-to five years old, participation in healthcare situations. We also describe the specific contributions of the children, who tested the prototypes in a preschool, a primary health care clinic and an outpatient unit at a hospital, during the development process. The iterative phases enabled the children to be involved at different stages of the process and to evaluate modifications and improvements made after each prior iteration. The children contributed their own perspectives (the child's perspective) on the usability, content and graphic design of the application, substantially improving the software and resulting in an age-appropriate product.

Ingenol mebutate gel for actinic keratosis: the link between quality of life, treatment satisfaction, and clinical outcomes.

BACKGROUND: Actinic keratosis therapy can elicit unsightly and painful local skin responses; assessment of treatment satisfaction and health-related quality of life (QoL) is important. Ingenol mebutate gel is a novel topical field therapy for actinic keratosis. OBJECTIVE: Post-hoc analyses were performed based on patient-reported outcomes from phase-III trials (n = 1005) to assess the effects of ingenol mebutate on QoL and the relationship between both QoL and treatment satisfaction, and degree of lesion clearance. METHODS: Patients received ingenol mebutate or vehicle for self-application to a 25-cm(2) contiguous area: 0.015% once daily for 3 consecutive days (face/scalp) or 0.05% once daily for 2 consecutive days (trunk/extremities). QoL (Skindex-16) and Treatment Satisfaction Questionnaire for Medication data were recorded. RESULTS: Significant, positive associations between Treatment Satisfaction Questionnaire for Medication score and degree of clearance were identified for patients in the face/scalp (effectiveness P < .0001 and global satisfaction P = .0002) and trunk/extremities (P < .0001 and P = .0014, respectively) groups. There was a significant association between Skindex-16 score and clearance for patients in the face/scalp group for change in symptoms (P = .0218), emotions (P = .0002), and overall Skindex-16 score (P = .0006) from baseline. LIMITATIONS: Clinical trial population findings may not be generalizable to clinical practice. CONCLUSION: Ingenol mebutate significantly improved patients' QoL and treatment satisfaction. Improvements were associated with higher degrees of actinic keratosis lesion clearance.

Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results.

INTRODUCTION: Cryosurgery is the most common treatment for actinic keratosis (AK) in the United States. Efficacy with cryosurgery is variable, and is a modality for treating individual, visible lesions while failing to treat subclinical lesions. METHODS: FIELD Study 1 (NCT01541553) is a phase 3, multicenter, randomized, double-blind study that evaluated the short- (11-week) and long- (12-month) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel, versus cryosurgery followed by vehicle. RESULTS: Overall, 329 patients were randomized to ingenol mebutate 0.015% gel (n=167) or vehicle (n=162) 3 weeks after cryosurgery. Baseline characteristics were balanced across groups. At week 11, complete clearance rate (100%) in the treatment area was higher for ingenol mebutate gel compared with vehicle (60.5% vs 49.4%, respectively; P=.04). Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel (82.7% vs 75.6%). A general reduction from baseline lesion count was observed 3 weeks after cryosurgery. Treatment after cryosurgery was well tolerated. CONCLUSIONS: Short-term (11-week) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone.

Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results.

INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery. METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months. RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P =.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P =.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment. CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.

Optimisation of trace mineral supplementation in diets for Atlantic salmon smolt with reference to holistic fish performance in terms of growth, health, welfare, and potential environmental impacts.

The aquafeed ingredient inventory is ever changing, from marine to plant based, and recently evolving to incorporate increasing amounts of low trophic, side stream and circular economy based raw materials, each one contributing with variable amounts and qualities of macro- and micronutrients. Meeting the micronutrient requirement of farmed fish for healthy and efficient growth under normal and challenging conditions is of paramount importance. In this study we run a trial based on a 2 × 4 factorial design with three replications for each dietary treatment, where Atlantic salmon smolt were fed one of 8 experimental diets supplemented with either organic or inorganic mineral premixes (copper, iron, manganese, selenium, and zinc) at four dietary inclusion levels. We saw a trend for higher growth rate in the organic mineral groups irrespective of the dietary mineral levels. Mineral digestibility was negatively correlated with increasing mineral supplementation levels for all tested minerals but Se which increased with the increasing supplementation in the inorganic and up to the 2nd inclusion level in the organic mineral groups. Increasing mineral supplementation affected retention efficiency of Zn, Mn, Cu and Fe while mineral source affected only the retention of Se which was higher in the organic mineral groups. Moreover, fish obtained higher EPA and DHA in their body and increased slaughter yield in the organic as compared to the inorganic mineral groups and corroborated that trace mineral inclusion levels play a key role on salmon fillet's technical quality. More effects from different origin and dietary inclusion levels of trace minerals were seen on fillet yield, fillet technical and nutritional quality, bone strength, skin morphology, organ mineralization and midgut transcriptome.

Treatment responder analysis in actinic keratosis: can it lead the way to individualized choice of treatment?

BACKGROUND: It is unclear if there are any distinct AK patient populations that might respond best to a given treatment. OBJECTIVE: To identify if a distinct subgroup of patients with AK might respond better to treatment with ingenol mebutate (IngMeb) versus diclofenac sodium (DS). METHODS: Complete clearance of AK and mean lesion reduction at end of first treatment course and week 17 were evaluated within subgroups. RESULTS: 502 patients (255 IngMeb; 247 DS) were included in the analysis. At week 17, complete clearance was achieved by more patients treated with IngMeb versus DS within the majority of patient subgroups, including patients with <6 lesions and ≥6 lesions at baseline, aged ≥65 years, males, females, Fitzpatrick skin types II and III, and facial lesions. Mean lesion reduction at week 17 was greater with IngMeb than DS within the same subgroups, and in patients with scalp lesions. CONCLUSIONS: This responder analysis did not identify any distinct population that responded more optimally than others with IngMeb or DS. More patients achieved complete clearance and higher lesion reduction of AK with IngMeb compared with DS in most subgroups.

Optimization of N-methyl-N-[tert-butyldimethylsilyl]trifluoroacetamide as a derivatization agent for determining isotopic enrichment of glycerol in very-low density lipoproteins.

Stable isotope kinetic studies play an important role in the study of very-low density lipoprotein (VLDL) metabolism, including basic and clinical research. Today, [1,1,2,3,3-(2)H(5)]glycerol is the most cost-effective alternative to measure glycerol and triglyceride kinetics. Recycling of glycerol from glycolysis and gluconeogenesis may lead to incompletely labelled tracer molecules. Many existing methods for the measurement of glycerol isotopic enrichment involve the production of glycerol derivatives that result in fragmentation of the glycerol molecule after ionization. It would be favourable to measure the intact tracer molecule since incompletely labelled tracer molecules may be measured as fully labelled. The number of methods available to measure the intact tracer in biological samples is limited. The aim of this project was to develop a gas chromatography/mass spectrometry (GC/MS) method for glycerol enrichment that measures the intact glycerol backbone and is suitable for electron ionization (EI), which is widely available. A previously published method for N-methyl-N-[tert-butyldimethylsilyl]trifluoroacetamide (MTBSTFA) derivatization was significantly improved; we produced a stable derivative and increased recovery 27-fold in standards. We used the optimized MTBSTFA method in VLDL-triglyceride and found that further modification was required to take matrix effects into account. We now have a robust method to measure glycerol isotopic enrichment by GC/EI-MS that can be used to rule out the known problem of tracer recycling in studies of VLDL kinetics.

Helicobacter pylori binding to new glycans based on N-acetyllactosamine.

Previously we reported binding of Helicobacter pylori to various nonacid and sialylated neolacto carbohydrate structures using a wide range of natural and chemically modified sequences. A novel nonsialylated neolacto-based binding epitope, GlcNAc beta 3Gal beta 4GlcNAc, and analogous structures carrying terminal GalNAc beta 3, GalNAc alpha 3, or Gal alpha 3 showed the binding activity (Miller-Podraza H, Lanne B, Angström J, Teneberg S, Abul-Milh M, Jovall P-A, Karlsson H, Karlsson K-A. 2005. Novel binding epitope for Helicobacter pylori found in neolacto carbohydrate chains. J Biol Chem. 280:19695-19703). The present work reports two other H. pylori-binding nonsialylated neolacto-based structures, GlcA beta 3Gal beta 4GlcNAc beta 3-R and Glc beta 3Gal beta 4GlcNAc beta 3-R, and two amide derivatives (N-methyl and N-ethyl) of GlcA beta 3Gal beta 4GlcNAc beta 3-R which were bound by H. pylori. The latter structures turned out to be more effective as H. pylori binders than the parent saccharide. New reducing-end variants of the neolacto epitope including species containing N-acetyllactosamine linked beta 6 to GlcNAc or Gal with similarity to branched polylactosamines and mucins were prepared and tested. The results extend our previous findings on binding specificities of H. pylori and show that this pathogen is able to interact with an array of N-acetyllactosamine/neolacto structures, which may be of importance for the in vivo interaction of the bacterium with human cells. The information gained in this work may also be of value for rational design of anti-H. pylori drugs.

The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial.

BACKGROUND: Airway absorption and bioavailability of inhaled corticosteroids (ICSs) may be influenced by differences in pharmacokinetic properties such as lipophilicity and patient characteristics such as lung function. This study aimed to further investigate and clarify the distribution of budesonide and fluticasone in patients with severe chronic obstructive pulmonary disease (COPD) by measuring the systemic availability and sputum concentration of budesonide and fluticasone, administered via combination inhalers with the respective long-acting beta2-agonists, formoterol and salmeterol. METHODS: This was a randomized, double-blind, double-dummy, two-way crossover, multicenter study. Following a run-in period, 28 patients with severe COPD (mean age 65 years, mean forced expiratory volume in 1 second [FEV1] 37.5% predicted normal) and 27 healthy subjects (mean age 31 years, FEV1 103.3% predicted normal) received two single-dose treatments of budesonide/formoterol (400/12 microg) and salmeterol/fluticasone (50/500 microg), separated by a 4-14-day washout period. ICS concentrations were measured over 10 hours post-inhalation in plasma in all subjects, and over 6 hours in spontaneously expectorated sputum in COPD patients. The primary end point was the area under the curve (AUC) of budesonide and fluticasone plasma concentrations in COPD patients relative to healthy subjects. RESULTS: Mean plasma AUC values were lower in COPD patients versus healthy subjects for budesonide (3.07 microM x hr versus 6.21 microM x hr) and fluticasone (0.84 microM x hr versus 1.50 microM x hr), and the dose-adjusted AUC (geometric mean) ratios in healthy subjects and patients with severe COPD for plasma budesonide and fluticasone were similar (2.02 versus 1.80; primary end point). In COPD patients, the Tmax and the mean residence time in the systemic circulation were shorter for budesonide versus fluticasone (15.5 min versus 50.8 min and 4.41 hrs versus 12.78 hrs, respectively) and Cmax was higher (1.08 microM versus 0.09 microM). The amount of expectorated fluticasone (percentage of estimated lung-deposited dose) in sputum over 6 hours was significantly higher versus budesonide (ratio 5.21; p = 0.006). Both treatments were well tolerated. CONCLUSION: The relative systemic availabilities of budesonide and fluticasone between patients with severe COPD and healthy subjects were similar. In patients with COPD, a larger fraction of fluticasone was expectorated in the sputum as compared with budesonide. TRIAL REGISTRATION: Trial registration number NCT00379028.

Using an interactive communication tool in healthcare situations: Patterns in young children's use of participation cues.

This study forms part of a larger project about developing and using interactive technology to facilitate young children's participation in healthcare situations. Children's participation in these situations improves their motivation and situated understanding. Likewise, their participation helps professionals to more fully understand the child's perspective. In the project, an interactive communication tool, that is, an application suitable for tablet use, was developed with children, aged three to five, in two clinical settings. When tested, the children's participation cues, identified from video recordings of healthcare situations, were understood as having curious, thoughtful or affirmative meanings. This study aimed to investigate the similarities and differences in the young children's use of participation cues when using an interactive communication tool in healthcare situations. A secondary analysis of the identified cues was performed focusing on age, setting and examination or procedure. In total, 2167 cues were identified representing either curious, thoughtful or affirmative cues. The curious cues were mainly used (66%), followed by thoughtful (28%) and affirmative (6%) cues. Differences in cue usage were seen in relation to the children's age and setting. Knowing how children may react to common healthcare procedures may help increase healthcare professionals' awareness of the need to support children in an individual and situational way.

Purification and properties of major midgut leucyl aminopeptidase of Morimus funereus (Coleoptera, Cerambycidae) larvae.

The major leucyl aminopeptidase (LAP) from the midgut of Morimus funereus larvae was purified and characterised. Specific LAP activity was increased 292-fold by purification of the crude midgut extract. The purified enzyme had a pH optimum of 7.5 (optimum pH range 7.0-8.5) and preferentially hydrolysed p-nitroanilides containing hydrophobic amino acids in the active site, with the highest V(max)/K(M) ratio for leucine-p-nitroanilide (LpNA). Among a number of inhibitors tested, the most efficient were 1,10-phenanthroline having a K(i) value of 0.12 mM and cysteine with K(i) value of 0.31 mM, while EGTA stimulated LAP activity. Zn(2+), Mg(2+) and Mn(2+) all showed bi-modal effects on LAP activity (activated at low concentrations and inhibited at high concentrations). The purified LAP (after gel filtration on Superose 6 column) had molecular mass of 400 kDa with an isoelectric point of 6.2. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed one band of 67 kDa, suggesting that the enzyme is a hexamer. Six peptide sequences from protein band were obtained using ESI/MS-MS analysis. Comparison of the obtained peptide sequences with the EMBL-EBI sequence analysis toolbox and the BLASTP database showed a high degree of identity with other insect aminopeptidases.

Adaptive Collision Culling for Massive Simulations by a Parallel and Context-Aware Sweep and Prune Algorithm.

We present an improved parallel Sweep and Prune algorithm that solves the dynamic box intersection problem in three dimensions. It scales up to very large datasets, which makes it suitable for broad phase collision detection in complex moving body simulations. Our algorithm gracefully handles high-density scenarios, including challenging clustering behavior, by using a double-axis sweeping approach and a cache-friendly succinct data structure. The algorithm is realized by three parallel stages for sorting, candidate generation, and object pairing. By the use of temporal coherence, our sorting stage runs with close to optimal load balancing. Furthermore, our approach is characterized by a work-division strategy that relies on adaptive partitioning, which leads to almost ideal scalability. In addition, for scenarios that involves intense clustering along several axes simultaneously, we propose an enhancement that increases the context-awareness of the algorithm. By exploiting information gathered along three orthogonal axes, an efficient choice of what range query to perform can be made per object during run-time. Experimental results show high performance for up to millions of objects on modern multi-core CPUs.

The G protein-coupled receptor subset of the chicken genome.

G protein-coupled receptors (GPCRs) are one of the largest families of proteins, and here we scan the recently sequenced chicken genome for GPCRs. We use a homology-based approach, utilizing comparisons with all human GPCRs, to detect and verify chicken GPCRs from translated genomic alignments and Genscan predictions. We present 557 manually curated sequences for GPCRs from the chicken genome, of which 455 were previously not annotated. More than 60% of the chicken Genscan gene predictions with a human ortholog needed curation, which drastically changed the average percentage identity between the human-chicken orthologous pairs (from 56.3% to 72.9%). Of the non-olfactory chicken GPCRs, 79% had a one-to-one orthologous relationship to a human GPCR. The Frizzled, Secretin, and subgroups of the Rhodopsin families have high proportions of orthologous pairs, although the percentage of amino acid identity varies. Other groups show large differences, such as the Adhesion family and GPCRs that bind exogenous ligands. The chicken has only three bitter Taste 2 receptors, and it also lacks an ortholog to human TAS1R2 (one of three GPCRs in the human genome in the Taste 1 receptor family [TAS1R]), implying that the chicken's ability and mode of detecting both bitter and sweet taste may differ from the human's. The chicken genome contains at least 229 olfactory receptors, and the majority of these (218) originate from a chicken-specific expansion. To our knowledge, this dataset of chicken GPCRs is the largest curated dataset from a single gene family from a non-mammalian vertebrate. Both the updated human GPCR dataset, as well the chicken GPCR dataset, are available for download.