Understanding the clinical reasoning processes involved in the management of multimorbidity in an ambulatory setting: study protocol of a stimulated recall research.

BACKGROUND: Primary care physicians are at the very heart of managing patients suffering from multimorbidity. However, several studies have highlighted that some physicians feel ill-equipped to manage these kinds of complex clinical situations. Few studies are available on the clinical reasoning processes at play during the long-term management and follow-up of patients suffering from multimorbidity. This study aims to contribute to a better understanding on how the clinical reasoning of primary care physicians is affected during follow-up consultations with these patients. METHODS: A qualitative research project based on semi-structured interviews with primary care physicians in an ambulatory setting will be carried out, using the video stimulated recall interview method. Participants will be filmed in their work environment during a standard consultation with a patient suffering from multimorbidity using a "button camera" (small camera) which will be pinned to their white coat. The recording will be used in a following semi-structured interview with physicians and the research team to instigate a stimulated recall. Stimulated recall is a research method that allows the investigation of cognitive processes by inviting participants to recall their concurrent thinking during an event when prompted by a video sequence recall. During this interview, participants will be prompted by different video sequence and asked to discuss them; the aim will be to encourage them to make their clinical reasoning processes explicit. Fifteen to twenty interviews are planned to reach data saturation. The interviews will be transcribed verbatim and data will be analysed according to a standard content analysis, using deductive and inductive approaches. CONCLUSION: Study results will contribute to the scientific community's overall understanding of clinical reasoning. This will subsequently allow future generation of primary care physicians to have access to more adequate trainings to manage patients suffering from multimorbidity in their practice. As a result, this will improve the quality of the patient's care and treatments.

The association of dietary animal and plant protein with putative risk markers of colorectal cancer in overweight pre-diabetic individuals during a weight-reducing programme: a PREVIEW sub-study.

PURPOSE: Diets with increased protein content are popular strategies for body weight regulation, but the effect of such diets for the colonic luminal environment is unclear. We aimed to investigate the associations between putative colorectal cancer-related markers and total protein intake, plant and animal proteins, and protein from red and processed meat in pre-diabetic adults (> 25 years). METHODS: Analyses were based on clinical and dietary assessments at baseline and after 1 year of intervention. Protein intake was assessed from 4-day dietary records. Putative colorectal cancer-related markers identified from 24-h faecal samples collected over three consecutive days were: concentration of short-chain fatty acids, phenols, ammonia, and pH. RESULTS: In total, 79 participants were included in the analyses. We found a positive association between change in total protein intake (slope: 74.72 ± 28.84 µmol per g faeces/E%, p = 0.01), including animal protein intake (slope: 87.63 ± 32.04 µmol per g faeces/E%, p = 0.009), and change in faecal ammonia concentration. For change in ammonia, there was a dose-response trend from the most negative (lowest tertile) to the most positive (highest tertile) association (p = 0.01): in the high tertile, a change in intake of red meat was positively associated with an increase in ammonia excretion (slope: 2.0 ± 0.5 µmol per g faeces/g/day, p < 0.001), whereas no such association was found in the low and medium tertile groups. CONCLUSION: Increases in total and animal protein intakes were associated with higher excretion of ammonia in faeces after 1 year in overweight pre-diabetic adults undertaking a weight-loss intervention. An increase in total or relative protein intake, or in the ratio of animal to plant protein, was not associated with an increase in faeces of any of the other putative colorectal cancer risk markers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01777893.

Multiple and asymmetrical origin of polyploid dog rose hybrids (Rosa L. sect. Caninae (DC.) Ser.) involving unreduced gametes.

Background and Aims: Polyploidy and hybridization are important factors for generating diversity in plants. The species-rich dog roses ( Rosa sect. Caninae ) originated by allopolyploidy and are characterized by unbalanced meiosis producing polyploid egg cells (usually 4 x ) and haploid sperm cells (1 x ). In extant natural stands species hybridize spontaneously, but the extent of natural hybridization is unknown. The aim of the study was to document the frequency of reciprocal hybridization between the subsections Rubigineae and Caninae with special reference to the contribution of unreduced egg cells (5 x ) producing 6 x offspring after fertilization with reduced (1 x ) sperm cells. We tested whether hybrids arose by independent multiple events or via a single or few incidences followed by a subsequent spread of hybrids. Methods: Population genetics of 45 mixed stands of dog roses across central and south-eastern Europe were analysed using microsatellite markers and flow cytometry. Hybrids were recognized by the presence of diagnostic alleles and multivariate statistics were used to display the relationships between parental species and hybrids. Key Results: Among plants classified to subsect. Rubigineae , 32 % hybridogenic individuals were detected but only 8 % hybrids were found in plants assigned to subsect. Caninae . This bias between reciprocal crossings was accompanied by a higher ploidy level in Rubigineae hybrids, which originated more frequently by unreduced egg cells. Genetic patterns of hybrids were strongly geographically structured, supporting their independent origin. Conclusions: The biased crossing barriers between subsections are explained by the facilitated production of unreduced gametes in subsect. Rubigineae . Unreduced egg cells probably provide the highly homologous chromosome sets required for correct chromosome pairing in hybrids. Furthermore, the higher frequency of Rubigineae hybrids is probably influenced by abundance effects because the plants of subsect. Caninae are much more abundant and thus provide large quantities of pollen. Hybrids are formed spontaneously, leading to highly diverse mixed stands, which are insufficiently characterized by the actual taxonomy.

Use of nutritional supplements by Danish elite athletes and fitness customers.

The nutritional supplement (NS) industry is one of the fastest growing in the world, and NS use in Denmark is among the highest in Europe. However, the exact use in elite athletes and fitness customers targeted for doping control is unknown. Information from 634 doping control forms obtained in 2014 was evaluated (elite athletes: n = 361; fitness customers: n = 273). The majority of female (92.6%) and male (85.0%) elite athletes and female (100.0%) and male (94.0%) fitness customers declared using one or more NS. The use of non-ergogenic NS was more prevalent in women than in men and in younger (15-34 years) compared with older (35-49 years) subjects, but it was less prevalent in intermittent compared with endurance and power/strength sports. Additionally, fitness customers who tested positive for doping also reported using more NS than subjects testing negative, indicating an association between NS and doping abuse. The present results demonstrate a very high prevalence of NS usage in both elite athletes and fitness customers. This highlights the importance of a strong national regulation of NS to avoid contamination of NS with doping substances.

Acute exercise and motor memory consolidation: Does exercise type play a role?

A single bout of high-intensity exercise can augment off-line gains in skills acquired during motor practice. It is currently unknown if the type of physical exercise influences the effect on motor skill consolidation. This study investigated the effect of three types of high-intensity exercise following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill were performed 1 (R1h) and 24 h (R1d) post acquisition. For all exercise groups, mean motor performance scores decreased at R1h compared to post acquisition (POST) level; STR (P = 0.018), CT (P = 0.02), HOC (P = 0.014) and performance scores decreased for CT compared to CON (P = 0.049). Mean performance scores increased from POST to R1d for all exercise groups; STR (P = 0.010), CT (P = 0.020), HOC (P = 0.007) while performance scores for CON decreased (P = 0.043). Changes in motor performance were thus greater for STR (P = 0.006), CT (P < 0.001) and HOC (P < 0.001) compared to CON from POST to R1d. The results demonstrate that high-intensity, acute exercise can lead to a decrease in motor performance assessed shortly after motor skill practice (R1h), but enhances offline effects promoting long-term retention (R1d). Given that different exercise modalities produced similar positive off-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed.

Simultaneous inference of a binary composite endpoint and its components.

Binary composite endpoints offer some advantages as a way to succinctly combine evidence from a number of related binary endpoints recorded in the same clinical trial into a single outcome. However, as some concerns about the clinical relevance as well as the interpretation of such composite endpoints have been raised, it is recommended to evaluate the composite endpoint jointly with the involved components. We propose an approach for carrying out simultaneous inference based on separate model fits for each endpoint, yet controlling the familywise type I error rate asymptotically. The key idea is to stack parameter estimates from the different fits and derive their joint asymptotic distribution. Simulations show that the proposed approach comes closer to nominal levels and has comparable or higher power as compared to existing approaches, even for moderate sample sizes (around 100-200 observations). The method is compared to the gatekeeping approach and results are provided in the Supplementary Material. In two data examples we show how the procedure may be adapted to handle local significance levels specified through a priori given weights.

Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial.

OBJECTIVES: Increased energy expenditure (EE) has been proposed as an important mechanism for weight loss following Roux-en-Y gastric bypass (RYGB). However, this has never been investigated in a controlled setting independent of changes in energy balance. Similarly, only few studies have investigated the effect of RYGB on glycaemic control per se. Here, we investigated the effect of RYGB on EE, appetite, glycaemic control and specific signalling molecules compared with a control group in comparable negative energy balance. SUBJECTS/METHODS: Obese normal glucose-tolerant participants were randomized to receive RYGB after 8 (n=14) or 12 weeks (n=14). The protocol included a visit at week 0 and three visits (weeks 7, 11 and 78) where 24-h EE, appetite and blood parameters were assessed. Participants followed a low-calorie diet from weeks 0-11, with those operated at week 12 serving as a control group for those operated at week 8. RESULTS: Compared with controls, RYGB-operated participants had lower body composition-adjusted 24-h EE and basal EE 3 weeks postoperatively (both P<0.05) but EE parameters at week 78 were not different from preoperative values (week 7). Surgery changed the postprandial response of glucagon-like peptide-1 (GLP-1), peptide YY3-36 (PYY), ghrelin, cholecystokinin, fibroblast growth factor-19 and bile acids (all P<0.05). Particularly, increases in GLP-1, PYY and decreases in ghrelin were associated with decreased appetite. None of HOMA-IR (homeostasis model assessment-estimated insulin resistance), Matsuda index, the insulinogenic index, the disposition index and fasting hepatic insulin clearance were different between the groups, but RYGB operated had lower fasting glucose (P<0.05) and the postprandial glucose profile was shifted to the left (P<0.01). CONCLUSIONS: Our data do not support that EE is increased after RYGB. More likely, RYGB promotes weight loss by reducing appetite, partly mediated by changes in gastrointestinal hormone secretion. Furthermore, we found that the early changes in glycaemic control after RYGB is to a large extent mediated by caloric restriction.

Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children.

UNLABELLED: We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely associated with bone size in girls. INTRODUCTION: Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin, adiponectin, leptin, insulin, insulin-like growth factor-I (IGF-1), osteocalcin, and intact parathyroid hormone, and subsequent changes in height and in whole-body height-adjusted bone area "BAheight" and size-adjusted bone mineral content "BMCsize" in 8- to 11-year-olds. METHODS: Analyses were carried out separately for boys (n = 325) and girls (n = 308) including data from baseline, 3 and 6 months from OPUS School Meal Study. RESULTS: In both sexes: gain in BAheight was positively associated with baseline FM (≥2.05 cm(2)/kg, both p ≤ 0.003). Furthermore, gain in height was positively associated with baseline IGF-1 (≥0.02 cm/ng/ml, p = 0.001) and osteocalcin (≥0.13 cm/ng/ml, p ≤ 0.009); and gain in BAheight was positively associated with baseline osteocalcin (≥0.35 cm(2)/ng/ml, p ≤ 0.019). In girls only, gain in BAheight was also positively associated with baseline IGF-1 (0.06 cm(2)/ng/ml, p = 0.017) and inversely associated with both baseline ghrelin (-0.01 cm(2)/pg/ml, p = 0.001) and leptin (-1.21 cm(2)/µg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18 g/ng/ml, p = 0.030). CONCLUSIONS: This large longitudinal study suggests that in 8- to 11-year-old children, IGF-1 and osteocalcin predict growth in height, while FM, osteocalcin, and in girls also, IGF-1 predict growth in BAheight. Fat-independent inverse associations of leptin and ghrelin with BAheight in girls' are contrary to proposed growth-stimulating effects of leptin. Osteocalcin in boys predicts gain in BMCsize.

Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial.

BACKGROUND: The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder. METHOD: A total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups. RESULTS: Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group. CONCLUSIONS: These results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool.

Characterization and scoring of skin changes in severe acute malnutrition in children between 6 months and 5 years of age.

BACKGROUND: Severe acute malnutrition is a life-threatening condition. It can be associated with severe skin changes, first properly described by Williams in 1933. The aetiology of these skin changes is still unknown and their character has never been systematically described in dermatological terms. The skin changes have been shown to be a predictor of mortality in hospital care. Systematic investigations on the character of the skin changes that have effect on prognosis, are needed to investigate which of the skin changes that are relevant to improve treatment. OBJECTIVES: Our main objective was to identify the skin changes characteristic of children with severe acute malnutrition and to develop a clinical score that describes the morphology and severity in dermatological terms. We also investigated if any of the different skin changes were connected to prognosis. MATERIALS AND METHODS: At Mulago Hospital, Mwanamugimu (Department of Paediatrics and Child Health), Uganda, 120 children were included over a period of six months and observed when treated for severe acute malnutrition. Skin changes were registered through clinical examination and photo documentation and associated to prognosis using Cox and logistic regression analysis. RESULTS: Skin manifestations were characterized by five objective skin signs: telogenic effluvium, pigmentary changes (hyper- and hypo-pigmentation), ichthyosiform skin changes, lichenoid skin changes and bullae-erosion-desquamation. The skin changes could be registered in a systematic manner using our simple clinical score. Lichenoid skin changes were a significant predictor of death and allowed improved accuracy of prediction of mortality. CONCLUSIONS: The clinical score is simple and practical. A standardized way to register and score the skin changes, will allow a more unified way of reporting results in future studies. The standardization of observations, obtained through the proposed scoring system, will enable comparison of study results in the future.

Concordant or discordant results by the tuberculin skin test and the quantiFERON-TB test in children reflect immune biomarker profiles.

The tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-tube (QFTGIT) are adjunctive tests used in the diagnosis of pediatric tuberculosis (TB). Neither test can rule out TB; however, a positive test usually triggers preventive treatment in TB contacts aged <5 years. TST and QFTGIT can give divergent results and it is unclear how discordant results should be interpreted in terms of TB risk and preventive treatment. To understand the immune processes underlying concordant or discordant TST and QFTGIT results, we analyzed immune responses in children from Palamaner Taluk in India (a TB-endemic region with routine neonatal BCG vaccination) who were referred to a TB case verification ward on suspicion of TB. Two hundred and ten children aged <3 years were classified according to their TST and QFTGIT results, and their immune responses analyzed by dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification, using a panel of 45 genes and a 10-plex antigen-specific enzyme-linked immunosorbent assay. We show that immune biomarkers FPR1, TNFRSF1A and interferon (IFN)-γ are upregulated (all P<0.05) in concordant test-positive children, whereas BPI is downregulated (P<0.05). In contrast, SEC14L1 (P=0.034) and Interferon gamma-induced protein 10 (IP-10) (P=0.001) are differentially expressed between the TST+QFTGIT- /TST-QFTGIT+ groups. Known TB exposure was more frequent in concordant positive children and results were consistent with elevated expression of genes associated with inflammatory responses. Children with discordant test results displayed a mixed profile with activation of both pro- and anti-inflammatory markers. TST and/or QFTGIT positivity appears to reflect distinct but overlapping aspects of host immunity.

Novel method to identify the optimal antimicrobial peptide in a combination matrix, using anoplin as an example.

Microbial resistance is an increasing health concern and a true danger to human well-being. A worldwide search for new compounds is ongoing, and antimicrobial peptides are promising lead candidates for tomorrow's antibiotics. The decapeptide anoplin (GLLKRIKTLL-NH2) is an especially interesting candidate because of its small size as well as its antimicrobial and nonhemolytic properties. Optimization of the properties of an antimicrobial peptide such as anoplin requires multidimensional searching in a complex chemical space. Typically, such optimization is performed by labor-intensive and costly trial-and-error methods. In this study, we show the benefit of fractional factorial design for identification of the optimal antimicrobial peptide in a combination matrix. We synthesized and analyzed a training set of 12 anoplin analogs, representative of 64 analogs in total. Using MIC, hemolysis, and high-performance liquid chromatography retention time data, we constructed analysis-of-variance models that describe the relationship between these properties and the structural characteristics of the analogs. We show that the mathematical models derived from the training set data can be used to predict the properties of other analogs in the chemical space. Hence, this method provides an efficient means of identification of the optimal peptide in the searched chemical space.

Fatness predicts decreased physical activity and increased sedentary time, but not vice versa: support from a longitudinal study in 8- to 11-year-old children.

OBJECTIVE: To examine independent and combined cross-sectional associations between movement behaviors (physical activity (PA), sedentary time, sleep duration, screen time and sleep disturbance) and fat mass index (FMI), as well as to examine longitudinal associations between movement behaviors and FMI. METHODS: Cross-sectional and longitudinal analyses were done using data from the OPUS school meal study on 785 children (52% boys, 13.4% overweight, ages 8-11 years). Total PA, moderate-to-vigorous PA (MVPA), sedentary time and sleep duration (7 days and 8 nights) were assessed by an accelerometer and FMI was determined by dual-energy X-ray absorptiometry (DXA) on three occasions over 200 days. Demographic characteristics, screen time and sleep disturbance (Children's Sleep Habits Questionnaire) were also obtained. RESULTS: Total PA, MVPA and sleep duration were negatively associated with FMI, while sedentary time and sleep disturbances were positively associated with FMI (P⩽0.01). However, only total PA, MVPA and sleep duration were independently associated with FMI after adjustment for multiple covariates (P<0.001). Nevertheless, combined associations revealed synergistic effects among the different movement behaviors. Changes over time in MVPA were negatively associated with changes in FMI (P<0.001). However, none of the movement behaviors at baseline predicted changes in FMI (P>0.05), but higher FMI at baseline predicted a decrease in total PA and MVPA, and an increase in sedentary time (P⩽0.001), even in normal-weight children (P⩽0.03). CONCLUSION: Total PA, MVPA and sleep duration were independently associated with FMI, and combined associations of movement behaviors showed a synergistic effect with FMI. In the longitudinal study design, a high FMI at baseline was associated with lower PA and higher sedentary time after 200 days but not vice versa, even in normal-weight children. Our results suggest that adiposity is a better predictor of PA and sedentary behavior changes than the other way around.

Growth, livability, feed consumption, and carcass composition of the Athens Canadian Random Bred 1955 meat-type chicken versus the 2012 high-yielding Cobb 500 broiler.

A flock of the Athens Canadian Random Bred (ACRB), a 1955 meat-type chicken control strain, was raised alongside a flock of 2012 Cobb 500 fast feathering high-yielding broilers to determine selection changes over the past 57 yr. All birds were reared under management practices appropriate for the Cobb 500. Birds were weighed weekly and processed at 6, 8, and 10 wk. Whole carcass, carcass parts, and organs were weighed. Modern broilers outweighed ACRB at every age, ranging from 3.7 to 4.7 times the size of the ACRB. All parts and organs were compared as a percentage of live fasted BW. The ACRB had significantly heavier feet, wings, internal organs, and feathers. The modern Cobb broiler had double the breast and larger leg muscles and had a significantly greater fat pad. Despite the larger muscle mass, the supply organs, the heart and lungs, were significantly smaller in the Cobb broiler than the ACRB as a percentage of BW. Relative size of supply and other vital organs should be given consideration for genetic selection of the future broiler. Comparisons of ACRB weights and organ percentages with past published data indicates that the ACRB remains a consistent control strain.

Identification of biomarkers for Mycobacterium tuberculosis infection and disease in BCG-vaccinated young children in Southern India.

Pediatric tuberculosis (TB) often goes undiagnosed because of the lack of reliable diagnostic methods. With the aim of assessing biomarker(s) that can aid in the diagnosis of TB infection and disease, we investigated 746 Indian children with suspected TB. Whole-blood mRNA from 210 children was examined by dual-color Reverse-Transcriptase Multiple Ligation-dependent Probe-Amplification for the expression of 45 genes and a Bio-Plex assay for the expression of cytokines/chemokines in QuantiFERON supernatants. The study shows that transcription of SEC14L1, GUSB, BPI, CCR7 and TGFß-1 (all P ≤ 0.05) was downregulated in TB disease compared with uninfected controls, while transcription of RAB33A was downregulated in TB disease compared with both latent TB (P < 0.05) and controls (P < 0.01). The transcription of CD4, TGFß-1 (P < 0.01) and the expression of IL-2 (P < 0.01) and IL-13 (P < 0.05) was upregulated in latent TB compared with that in controls. Using the Least Absolute Shrinkage and Selection Operator (lasso) model, RAB33A alone discriminated between TB disease and latent TB (area under the curve (AUC) 77.5%), whereas a combination of RAB33A, CXCL10, SEC14L1, FOXP3 and TNFRSF1A was effective in discriminating between TB disease and controls (AUC 91.7%). A combination of 11 biomarkers predicted latent TB with moderate discriminatory power (AUC 72.2%). In conclusion, RAB33A is a potential biomarker for TB disease, whereas CD4, TGFß-1 and IL-2, IL-13 may identify latent TB in children.

Acute effects of mustard, horseradish, black pepper and ginger on energy expenditure, appetite, ad libitum energy intake and energy balance in human subjects.

Chilli peppers have been shown to enhance diet-induced thermogenesis (DIT) and reduce energy intake (EI) in some studies, but there are few data on other pungent spices. The primary aim of the present study was to test the acute effects of black pepper (pepper), ginger, horseradish and mustard in a meal on 4 h postprandial DIT. The secondary aim was to examine the effects on subjective appetite measures, ad libitum EI and energy balance. In a five-way placebo-controlled, single-blind, cross-over trial, twenty-two young (age 24·9 (SD 4·6) years), normal-weight (BMI 21·8 (SD 2·1) kg/m²) males were randomly assigned to receive a brunch meal with either pepper (1·3 g), ginger (20 g), horseradish (8·3 g), mustard (21 g) or no spices (placebo). The amounts of spices were chosen from pre-testing to make the meal spicy but palatable. No significant treatment effects were observed on DIT, but mustard produced DIT, which tended to be larger than that of placebo (14 %, 59 (SE 3) v. 52 (SE 2) kJ/h, respectively, P=0·08). No other spice induced thermogenic effects approaching statistical significance. Subjective measures of appetite (P>0·85), ad libitum EI (P=0·63) and energy balance (P=0·67) also did not differ between the treatments. Finally, horseradish decreased heart rate (P=0·048) and increased diastolic blood pressure (P= 0·049) compared with placebo. In conclusion, no reliable treatment effects on appetite, EI or energy balance were observed, although mustard tended to be thermogenic at this dose. Further studies should explore the possible strength and mechanisms of the potential thermogenic effect of mustard actives, and potential enhancement by, for example, combinations with other food components.

Molecular phylogeny and character evolution in terete-stemmed Andean opuntias (Cactaceae-Opuntioideae).

The cacti of tribe Tephrocacteae (Cactaceae-Opuntioideae) are adapted to diverse climatic conditions over a wide area of the southern Andes and adjacent lowlands. They exhibit a range of life forms from geophytes and cushion-plants to dwarf shrubs, shrubs or small trees. To confirm or challenge previous morphology-based classifications and molecular phylogenies, we sampled DNA sequences from the chloroplast trnK/matK region and the nuclear low copy gene phyC and compared the resulting phylogenies with previous data gathered from nuclear ribosomal DNA sequences. The here presented chloroplast and nuclear low copy gene phylogenies were mutually congruent and broadly coincident with the classification based on gross morphology and seed micro-morphology and anatomy. Reconstruction of hypothetical ancestral character states suggested that geophytes and cushion-forming species probably evolved several times from dwarf shrubby precursors. We also traced an increase of embryo size at the expense of the nucellus-derived storage tissue during the evolution of the Tephrocacteae, which is thought to be an evolutionary advantage because nutrients are then more rapidly accessible for the germinating embryo. In contrast to these highly concordant phylogenies, nuclear ribosomal DNA data sampled by a previous study yielded conflicting phylogenetic signals. Secondary structure predictions of ribosomal transcribed spacers suggested that this phylogeny is strongly influenced by the inclusion of paralogous sequence probably arisen by genome duplication during the evolution of this plant group.

Tenacity of low-pathogenic avian influenza viruses in different types of poultry litter.

To determine the risk of infection associated with exposure to low-pathogenic avian influenza (AI) virus-contaminated poultry litter, the tenacity of low pathogenic A/Ck/CA/431/00(H6N2), A/Mallard/MN/355779/00(H5N2), and A/turkey/Ohio/313053/04(H3N2) was evaluated. Viral stocks were incubated with poultry litter from commercial flocks at 25°C. Three types of poultry litter, wood shavings, shavings plus gypsum, and shavings plus peanut hulls, from commercial broiler flocks were used. The 3 low-pathogenic avian influenza viruses retained infectivity for one day in wood shavings and shavings plus peanut hulls litter types, whereas in wood shavings plus gypsum, litter viruses remained infective for up to 3 d. In contrast to the survivability in litter, all the viruses maintained infectivity in water for 4 d at titers of log(10)4.5. The infectivity of A/Ck/CA/431/00(H6N2) shed by experimentally infected layers, broilers, and turkeys was retained for one day, independently of the type of litter. In commercial production where a high density of birds are housed, the viral load shed by an infected flock will be significantly higher than the viral load shed 3 d postinfection obtained under the experimental conditions used in this study. Therefore proper management and disposal of poultry by products, such as windrow composting of litter and the composting of carcasses during an AI outbreak should be implemented.

Rapid syndromic PCR testing in patients with respiratory tract infections reduces time to results and improves microbial yield.

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus, compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae, Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.

Explained variation in a fully specified model for data-grouped survival data.

An additive hazards model may be used to quantify the effect of genetic and environmental predictors on flowering of sugar beet plants recorded as data-grouped time-to-event data. Estimated predictor effects have an intuitive interpretation rooted in the underlying time dynamics of the flowering process. However, agricultural experiments are often designed using several plots containing a large number of plants that are subsequently being monitored. In this article, we consider an additive hazards model with an additional plot structure induced by latent shared frailty variables. This approach enables us to derive a method to assess the quality of predictors in terms of how much plot variation they explain. We apply the method to a large data set exploring flowering of sugar beet and conclude that the genetic predictor biotype, which has a strong effect, also explains a substantial amount of the plot variation. The method is also applied to a data set from medical research concerning days to virus positivity of serum samples in AIDS patients.