Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naïve individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA).

To the authors' knowledge, there is currently no literature or guidance recommendation regarding whether the dose of dolutegravir (DTG) should be increased when co-administered with darunavir/ritonavir (DRV/r) in patients with acute human immunodeficiency virus infection (AHI). This study assessed the pharmacokinetics (PK) of twice-daily (BID) DTG and once-daily (QD) DRV/r, and compared this with DTG QD without DRV/r in patients with AHI. Forty-six participants initiated antiretroviral therapy within <24 h of enrolment: DTG 50 mg BID, DRV/r 800/100 mg QD, and two nucleoside reverse transcriptase inhibitors (NRTIs) for 4 weeks (Phase I); and DTG 50 mg QD with two NRTIs thereafter (Phase II: reference). Total DTG trough concentration (Ctrough) and area under the concentration-time profile of 0-24 h (AUC0-24h) were predicted using a population PK model. DTG glucuronidation metabolic ratio (MR) and DTG free fraction were determined and compared per treatment phase using geometric mean ratio (GMR) and 90% confidence interval (CI). Participants had a predicted geometric mean steady-state DTG Ctrough of 2.83 [coefficient of variation (CV%) 30.3%] mg/L (Phase I) and 1.28 (CV% 52.4%) mg/L (Phase II), with GMR of 2.20 (90% CI 1.90-2.55). Total exposure during DTG BID increased but did not double [AUC0-24h GMR 1.65 (90% CI 1.50-1.81) h.mg/L]. DTG glucuronidation MR increased by approximately 29% during Phase I. DTG Ctrough was above in-vivo EC90 (0.32 mg/L) during both phases, except in one participant during Phase I. At Week 8, 84% of participants had viral loads ≤40 copies/mL. The drug-drug interaction between DTG (BID) and DRV/r (QD) was due to induced glucuronidation, and is not clinically relevant in patients with AHI.

Launching a multidisciplinary European collaboration towards a cure for HIV: The EU2Cure Consortium.

We felt the urgency to launch the EU2Cure Consortium to support research and find a cure for the human immunodeficiency virus (HIV) infection through intensified collaboration within Europe. This consortium is open to stakeholders on cure in Europe from academia and the community to connect. The aim of this consortium is to intensify the research collaboration amongst European HIV cure groups and the community and facilitate interactions with other academic and community cure consortia, private parties, and policy makers. Our main aim is to create a European research agenda, data sharing, and development of best practice for clinical and translational science to achieve breakthroughs with clinically feasible HIV cure strategies. This consortium should also enable setting up collaborative studies accessible to a broader group of people living with HIV. Besides reservoir studies, we have identified three overlapping scientific interests in the consortium that provide a starting point for further research within a European network: developing "shock and kill" cure strategies, defining HIV cure biomarkers, and connecting cure cohorts. This strategy should aid stakeholders to sustain progress in HIV cure research regardless of coincidental global health or political crises.

The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement.

OBJECTIVES: The dolutegravir/valproic acid drug-drug interaction (DDI) is suggested to be caused by protein displacement. Here, we assess the underlying mechanism. METHODS: Participants in a randomized controlled trial investigating valproic acid as an HIV latency reversing agent were recruited in a predefined pharmacokinetic substudy if they were on once-daily 50 mg dolutegravir-containing combination ART (cART) for >12 months with a plasma HIV-RNA <50 copies/mL (trial registration: ClinicalTrials.gov NCT03525730). Participants were randomized to receive 30 mg/kg/day valproic acid orally (divided into two equal doses) for 14 days or not. Total and unbound dolutegravir concentrations were measured on day 0 (before intake of valproic acid and 6 h after intake of valproic acid) and on days 1, 7, 14 and 42. Intra- and inter-subject dolutegravir concentrations and geometric means (GMs) were evaluated. RESULTS: Six of 10 participants on dolutegravir were randomized to receive valproic acid. During 14 days of valproic acid treatment, the GM total dolutegravir concentration decreased sharply from 1.36 mg/L on day 0 to 0.85, 0.31 and 0.20 mg/L on days 0, 1, 7 and 14, respectively, while total dolutegravir concentrations in the controls remained comparable during the same period: 1.27-1.49 mg/L. We observed a parallel increase in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. CONCLUSIONS: This study confirms protein displacement as the main mechanism for this DDI, although additional mechanisms might be involved too. If dolutegravir is taken with food, this DDI is probably not clinically relevant.

Inferring an animal's environment through biologging: quantifying the environmental influence on animal movement.

BACKGROUND: Animals respond to environmental variation by changing their movement in a multifaceted way. Recent advancements in biologging increasingly allow for detailed measurements of the multifaceted nature of movement, from descriptors of animal movement trajectories (e.g., using GPS) to descriptors of body part movements (e.g., using tri-axial accelerometers). Because this multivariate richness of movement data complicates inference on the environmental influence on animal movement, studies generally use simplified movement descriptors in statistical analyses. However, doing so limits the inference on the environmental influence on movement, as this requires that the multivariate richness of movement data can be fully considered in an analysis. METHODS: We propose a data-driven analytic framework, based on existing methods, to quantify the environmental influence on animal movement that can accommodate the multifaceted nature of animal movement. Instead of fitting a simplified movement descriptor to a suite of environmental variables, our proposed framework centres on predicting an environmental variable from the full set of multivariate movement data. The measure of fit of this prediction is taken to be the metric that quantifies how much of the environmental variation relates to the multivariate variation in animal movement. We demonstrate the usefulness of this framework through a case study about the influence of grass availability and time since milking on cow movements using machine learning algorithms. RESULTS: We show that on a one-hour timescale 37% of the variation in grass availability and 33% of time since milking influenced cow movements. Grass availability mostly influenced the cows' neck movement during grazing, while time since milking mostly influenced the movement through the landscape and the shared variation of accelerometer and GPS data (e.g., activity patterns). Furthermore, this framework proved to be insensitive to spurious correlations between environmental variables in quantifying the influence on animal movement. CONCLUSIONS: Not only is our proposed framework well-suited to study the environmental influence on animal movement; we argue that it can also be applied in any field that uses multivariate biologging data, e.g., animal physiology, to study the relationships between animals and their environment. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s40462-020-00228-4.

Effects of seasonality and previous logging on faecal helminth-microbiota associations in wild lemurs.

Gastrointestinal helminth-microbiota associations are shaped by various ecological processes. The effect of the ecological context of the host on the bacterial microbiome and gastrointestinal helminth parasites has been tested in a number of ecosystems and experimentally. This study takes the important step to look at these two groups at the same time and to start to examine how these communities interact in a changing host environment. Fresh faecal samples (N = 335) from eight wild Eulemur populations were collected over 2 years across Madagascar. We used 16S ribosomal RNA gene sequencing to characterise the bacterial microbiota composition, and faecal flotation to isolate and morphologically identify nematode eggs. Infections with nematodes of the genera Callistoura and Lemuricola occurred in all lemur populations. Seasonality significantly contributed to the observed variation in microbiota composition, especially in the dry deciduous forest. Microbial richness and Lemuricola spp. infection prevalence were highest in a previously intensely logged site, whereas Callistoura spp. showed no such pattern. In addition, we observed significant correlations between gastrointestinal parasites and bacterial microbiota composition in these lemurs, with 0.4-0.7% of the variation in faecal bacterial microbiota composition being explained by helminth infections. With this study, we show effects of environmental conditions on gastrointestinal nematodes and bacterial interactions in wild lemurs and believe it is essential to consider the potential role of microbiome-parasite associations on the hosts' GI stability, health, and survival.

Data verification of nationwide clinical quality registries.

Background: Clinical auditing is an emerging instrument for quality assessment and improvement. Moreover, clinical registries facilitate medical research as they provide 'real world' data. It is important that entered data are robust and reliable. The aim of this study was to describe the evolving procedure and results of data verification within the Dutch Institute for Clinical Auditing (DICA). Methods: Data verification performed on several (disease-specific) clinical registries between 2013 and 2015 was evaluated. Sign-up, sample size and process of verification were described. For each procedure, hospitals were visited by external data managers to verify registered data. Outcomes of data verification were completeness and accuracy. An assessment of the quality of data was given per registry, for each participating hospital. Using descriptive statistics, analyses were performed for different sections within the individual registries. Results: Seven of the 21 registries were verified, involving 174 visits to hospital departments. A step-by-step description of the data verification process was provided. Completeness of data in the registries varied from 97·2 to 99·4 per cent. Accuracy of data ranged from 88·2 to 100 per cent. Most discrepancies were observed for postoperative complications (0·7-7·5 per cent) and ASA classification (8·5-11·4 per cent). Data quality was assessed as 'sufficient' for 145 of the 174 hospital departments (83·3 per cent). Conclusion: Data verification revealed that the data entered in the observed DICA registries were complete and accurate.

Antecedentes: La auditoría clínica es un instrumento emergente para la evaluación y mejora de la calidad. Además, los registros clínicos facilitan la investigación médica ya que proporcionan datos de la "vida real". Es importante que los datos introducidos sean completos y fiables. El objetivo de este estudio fue describir la evolución y los resultados del procedimiento de verificación de datos en el seno del Instituto Holandés de Auditorias Clínicas (Dutch Institute for Clinical Auditing, DICA). Métodos: Se evaluó la verificación de datos realizada en varios registros clínicos (específicos de enfermedad) entre 2013­2015. Se describió el sistema de registro, tamaño de la muestra y el proceso de verificación. Para cada procedimiento, los hospitales fueron visitados por administradores de datos externos para verificar los datos registrados. Los resultados de la verificación de datos fueron la integridad y la exactitud. Se proporcionó una evaluación de la calidad de los datos para cada registro en cada uno de los hospitales que participaron. Mediante la utilización de estadística descriptiva, se realizaron análisis de diferentes secciones para cada uno de los registros. Resultados: Siete de los 21 registros fueron verificados, lo que implicó un total 174 visitas a los departamentos de los hospitales. Se proporcionó una descripción paso a paso del proceso de verificación de los datos. La integridad de los datos en los registros varió entre 97,3­99,4%. La exactitud de los datos varió entre 86,6­97,0%. La mayoría de las discrepancias se observaron en las complicaciones postoperatorias (0,7­7,5%) y clasificación ASA (7,5­11%). La calidad de los datos se consideró "suficiente" en 145 de 174 (83%) departamentos hospitalarios. Conclusión: La verificación de los datos reveló que la introducción de datos en los registros DICA analizados era bastante completa y exacta.

CRP-guided antibiotic treatment in acute exacerbations of COPD in hospital admissions.

The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD) is controversial and a biomarker identifying patients who benefit from antibiotics is mandatory. We performed a randomised, controlled trial in patients with acute exacerbations of COPD, comparing C-reactive protein (CRP)-guided antibiotic treatment to patient reported symptoms in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy, in order to show a reduction in antibiotic prescription.Patients hospitalised with acute exacerbations of COPD were randomised to receive antibiotics based either on the GOLD strategy or according to the CRP strategy (CRP ≥50 mg·L-1).In total, 101 patients were randomised to the CRP group and 119 to the GOLD group. Fewer patients in the CRP group were treated with antibiotics compared to the GOLD group (31.7% versus 46.2%, p=0.028; adjusted odds ratio (OR) 0.178, 95% CI 0.077-0.411, p=0.029). The 30-day treatment failure rate was nearly equal (44.5% in the CRP group versus 45.5% in the GOLD-group, p=0.881; adjusted OR 1.146, 95% CI 0.649-1.187, p=0.630), as was the time to next exacerbation (32 days in the CRP group versus 28 days in the GOLD group, p=0.713; adjusted hazard ratio 0.878, 95% CI 0.649-1.187, p=0.398). Length of stay was similar in both groups (7 days in the CRP group versus 6 days in the GOLD group, p=0.206). On day-30, no difference in symptom score, quality of life or serious adverse events was detected.Use of CRP as a biomarker to guide antibiotic treatment in severe acute exacerbations of COPD leads to a significant reduction in antibiotic treatment. In the present study, no differences in adverse events between both groups were found. Further research is needed for the generalisability of these findings.

Ending the epidemic: Critical role of primary HIV infection.

Early identification and immediate treatment of individuals newly infected with HIV is important for two reasons: it benefits the long-term health of the infected patient, and it reduces onward HIV transmission. Primary HIV infection (PHI) reflects the period following HIV acquisition during which viraemia bursts until the establishment of a stable plasma HIV-RNA level approximately six months post infection. During this period, patients are particularly contagious and are often unaware of the infection. As a consequence, PHI disproportionally affects onward transmission. During PHI the immune system is irreparably damaged and persistent viral reservoirs are formed. Initiating antiretroviral therapy (ART) during PHI could potentially lead to a functional cure through early and prolonged viral suppression. Unfortunately, symptoms of PHI are nonspecific and the diagnosis is frequently missed. This impedes timely diagnosis and prompt initiation of ART. To increase awareness and underscore the importance of immediate ART initiation, we describe here the pathogenesis, clinical presentation, and impact of treating PHI.

Disease transmission in animal transfer networks.

Infectious diseases transmission is strongly determined by who contacts whom. Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a worldwide burden for animal populations. One of the major transmission mechanism between herd is the transfer of infectious animal. In East Africa, pastoralists may receive or bestow livestock to create and strengthen social relationships. Here, we used a network approach to examine the relative importance of such cattle transfer in the transmission of bTB. First, a total of 2550 cattle from 102 herds were tested using the comparative intradermal tuberculin test to assess the presence of bTB infected cattle in the herd. A herd was considered bTB positive if it had at least one tuberculin reactor animal. Next, we calculated the centrality of each herd in the cattle transfer network using four established measures of social network centralization: degree, betweenness, closeness and fragmentation. The relationships between the network centrality measures and bTB infection were examined using generalized linear mixed models (GLMM). We found that a herd's in-degree in the social network was positively correlated with the risk of being infected with bTB (b=4.2, 95%CI=2.1-5.7; p<0.001). A herd that was close to many others (i.e., had a higher closeness index) had a larger chance of acquiring bTB infection (b=2.1, 95%CI=1.4-2.8; p<0.001). Betweenness centrality was also positively associated with the presence of bTB infection. There was a negative relationship between the fragmentation index and bTB infection (b=-2.7, 95%CI=-4.9-1.3; p<0.001). The study clearly demonstrated that the extent to which a herd is connected within a network has significant implications for its probability of being infected. Further, the results are in accordance with our expectation that connectivity and the probability that a herd will transmit the disease to other herds in the network are related.

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015.

Competition between a Lawn-Forming Cynodon dactylon and a Tufted Grass Species Hyparrhenia hirta on a South-African Dystrophic Savanna.

South African savanna grasslands are often characterised by indigestible tufted grass species whereas lawn grasses are far more desirable in terms of herbivore sustenance. We aimed to investigate the role of nutrients and/or the disturbance (grazing, trampling) by herbivores on the formation of grazing lawns. We conducted a series of common garden experiments to test the effect of nutrients on interspecific competition between a typical lawn-forming grass species (Cynodon dactylon) and a species that is frequently found outside grazing lawns (Hyparrhenia hirta), and tested for the effect of herbivore disturbance in the form of trampling and clipping. We also performed a vegetation and herbivore survey to apply experimentally derived insights to field observations. Our results showed that interspecific competition was not affected by soil nutrient concentrations. C. dactylon did show much more resilience to disturbance than H. hirta, presumably due to the regenerative capacity of its rhizomes. Results from the field survey were in line with these findings, describing a correlation between herbivore pressure and C. dactylon abundance. We conclude that herbivore disturbance, and not soil nutrients, provide C. dactylon with a competitive advantage over H. hirta, due to vegetative regeneration from its rhizomes. This provides evidence for the importance of concentrated, high herbivore densities for the creation and maintenance of grazing lawns.

Single-port laparoscopic appendectomy in children: single center experience in 50 patients.

BACKGROUND: Recent years evolution of minimal invasive laparoscopic procedures led to new techniques, like single-port laparoscopy (SPL), resulting in nearly-scarless procedures. The purpose of this study is to evaluate that SPL appendectomy is a safe and feasible procedure using a commercially available trocar (LESS: Laparo Endoscopic Single Site trocar; Olympus TriPort+) in pediatric patients. METHODS: From July 2011 to March 2014 all patients undergoing SPL appendectomy under 18 years were included in this retrospective study. Per- en postoperative data were collected in a prospective database. RESULTS: A total of 50 children (mean age 12 years) diagnosed as acute appendicitis underwent SPL appendectomy. SPL appendectomy was feasible and safe in all cases, both in non-perforated and perforated appendicitis. In one procedure (2%) an extra trocar was placed. Seven patients (14%) were readmitted to the hospital after initial uncomplicated postoperative course. One patient (2%) needed reoperation due to a wound abscess. Three patients (6%) were readmitted due to intra-abdominal abscesses for which antibiotics were given. CONCLUSIONS: SPL appendectomy is a safe and feasible procedure in children with acute appendicitis.

Antioxidants as a treatment for acute pancreatitis: A meta-analysis.

OBJECTIVE: To assess the efficacy of antioxidants in acute (AP) pancreatitis. METHODS: We searched PubMed, Embase and the Cochrane library for all randomized controlled trials (RCT) involving administration of antioxidants in the therapy of AP until February 2012. AP studies were pooled to analyze the effect of antioxidants on hospital stay, mortality, and complications. Subgroup analyses were performed on the use of the antioxidant glutamine. RESULTS: In total, eleven RCTs were included. Among patients with AP, antioxidant therapy resulted in a borderline significant reduction in hospital stay (mean difference -1.74; 95%CI -3.56 to 0.08), a significant decrease in complications (RR 0.66; 95%CI 0.46-0.95) and a non-significant decrease in mortality rate (RR 0.66; 95%CI 0.30-1.46). Subgroup analyses showed that glutamine significantly reduced complications (RR 0.51; 95%CI 0.34-0.78) and mortality rate (RR 0.33; 95%CI 0.13-0.85). CONCLUSION: The present meta-analysis shows a possible benefit of glutamine supplementation in patients with acute pancreatitis. However, large randomized trials are needed to confirm these observations.

Results of construction of protective loop ileostomies and reversal surgery for colorectal surgery.

BACKGROUND: Protective loop ileostomies in colorectal surgery are constructed to reduce morbidity and reinterventions related to the primary operation. However, ileostomies are associated with stoma-related morbidity and postoperative complications following reversal surgery. Dutch national data show increased use of loop ileostomies in colorectal surgery for cancer justifying an adequate assessment of its morbidity. This study was undertaken to investigate morbidity associated with protective loop ileostomies in colorectal surgery. METHODS: Retrospectively, 118 consecutive patients undergoing left-sided colonic or rectal resection with protective loop ileostomy were included. Primary outcome was 30-day mortality. Secondary endpoints included total complication rate (including stoma-related morbidity), total reintervention risk, anastomotic leakage risk and total length of stay. RESULTS: No mortality was observed. Overall major complication, reintervention and anastomotic leakage risk for colorectal surgery were 20, 20 and 3.9%, respectively. Combined length of stay for stoma-related morbidity and reversal surgery was 12.7 days. The risk for stoma-related morbidity was 35%, and the risk for nonelective reversal was 12%. Closure rate (mean follow-up of 15 months) was 87% with a mean interval of 125 days. Reversal surgery was not correlated with mortality but with major complications (11%) and reintervention risk, anastomotic leakage risk (3.8%) and a mean length of stay of 9 days. CONCLUSION: Construction of loop ileostomies in left-sided colonic or rectal resection is associated with a low risk for anastomotic leakage at the expense of substantial stoma-related morbidity and morbidity related to reversal surgery. More accurate identification of colorectal cancer patients benefitting from protective loop ileostomy seems to be warranted.

Dilution effect and identity effect by wildlife in the persistence and recurrence of bovine tuberculosis.

Current theories on disease-diversity relationships predict a strong influence of host richness on disease transmission. In addition, identity effect, caused by the occurrence of particular species, can also modify disease risk. We tested the richness effect and the identity effects of mammal species on bovine tuberculosis (bTB), based on the regional bTB outbreak data in cattle from 2005-2010 in Africa. Besides, we also tested which other factors were associated with the regional bTB persistence and recurrence in cattle. Our results suggested a dilution effect, where higher mammal species richness (MSR) was associated with reduced probabilities of bTB persistence and recurrence in interaction with cattle density. African buffalo had a positive effect on bTB recurrence and a positive interaction effect with cattle density on bTB persistence, indicating an additive positive identity effect of buffalo. The presence of greater kudu had no effect on bTB recurrence or bTB persistence. Climatic variables only act as risk factors for bTB persistence. In summary, our study identified both a dilution effect and identity effect of wildlife and showed that bTB persistence and recurrence were correlated with different sets of risk factors. These results are relevant for more effective control strategies and better targeted surveillance measures in bTB.

Larger antelopes are sensitive to heat stress throughout all seasons but smaller antelopes only during summer in an African semi-arid environment.

Heat stress can limit the activity time budget of ungulates due to hyperthermia, which is relevant for African antelopes in ecosystems where temperature routinely increases above 40 °C. Body size influences this thermal sensitivity as large bodied ungulates have a lower surface area to volume ratio than smaller ungulates, and therefore a reduced heat dissipation capacity. We tested whether the activity pattern during the day of three antelope species of different body size-eland, blue wildebeest and impala-is negatively correlated with the pattern of black globe temperature (BGT) during the day of the ten hottest days and each season in a South African semi-arid ecosystem. Furthermore, we tested whether the larger bodied eland and wildebeest are less active than the smaller impala during the hottest days and seasons. Our results show that indeed BGT was negatively correlated with the diurnal activity of eland, wildebeest and impala, particularly during summer. During spring, only the activity of the larger bodied eland and wildebeest was negatively influenced by BGT, but not for the smallest of the three species, the impala. We argue that spring, with its high heat stress, coupled with poor forage and water availability, could be critical for survival of these large African antelopes. Our study contributes to understanding how endothermic animals can cope with extreme climatic conditions, which are expected to occur more frequently due to climate change.

Genetic consequences of breaking migratory traditions in barnacle geese Branta leucopsis.

Cultural transmission of migratory traditions enables species to deal with their environment based on experiences from earlier generations. Also, it allows a more adequate and rapid response to rapidly changing environments. When individuals break with their migratory traditions, new population structures can emerge that may affect gene flow. Recently, the migratory traditions of the Barnacle Goose Branta leucopsis changed, and new populations differing in migratory distance emerged. Here, we investigate the population genetic structure of the Barnacle Goose to evaluate the consequences of altered migratory traditions. We used a set of 358 single nucleotide polymorphism (SNP) markers to genotype 418 individuals from breeding populations in Greenland, Spitsbergen, Russia, Sweden and the Netherlands, the latter two being newly emerged populations. We used discriminant analysis of principal components, FST , linkage disequilibrium and a comparison of geneflow models using migrate-n to show that there is significant population structure, but that relatively many pairs of SNPs are in linkage disequilibrium, suggesting recent admixture between these populations. Despite the assumed traditions of migration within populations, we also show that genetic exchange occurs between all populations. The newly established nonmigratory population in the Netherlands is characterized by high emigration into other populations, which suggests more exploratory behaviour, possibly as a result of shortened parental care. These results suggest that migratory traditions in populations are subject to change in geese and that such changes have population genetic consequences. We argue that the emergence of nonmigration probably resulted from developmental plasticity.

[Rapid prototyping: a very promising method]. / Rapid prototyping: een veelbelovende methode.

Rapid prototyping is a method which makes it possible to produce a three-dimensional model based on two-dimensional imaging. Various rapid prototyping methods are available for modelling, such as stereolithography, selective laser sintering, direct laser metal sintering, two-photon polymerization, laminated object manufacturing, three-dimensional printing, three-dimensional plotting, polyjet inkjet technology,fused deposition modelling, vacuum casting and milling. The various methods currently being used in the biomedical sector differ in production, materials and properties of the three-dimensional model which is produced. Rapid prototyping is mainly usedforpreoperative planning, simulation, education, and research into and development of bioengineering possibilities.