Arena3D: visualizing time-driven phenotypic differences in biological systems

<p>Abstract</p> <p>Background</p> <p>Elucidating the genotype-phenotype connection is one of the big challenges of modern molecular biology. To fully understand this connection, it is necessary to consider the underlying networks and the time factor. In this context of data deluge and heterogeneous information, visualization plays an essential role in interpreting complex and dynamic topologies. Thus, software that is able to bring the network, phenotypic and temporal information together is needed. Arena3D has been previously introduced as a tool that facilitates link discovery between processes. It uses a layered display to separate different levels of information while emphasizing the connections between them. We present novel developments of the tool for the visualization and analysis of dynamic genotype-phenotype landscapes.</p> <p>Results</p> <p>Version 2.0 introduces novel features that allow handling time course data in a phenotypic context. Gene expression levels or other measures can be loaded and visualized at different time points and phenotypic comparison is facilitated through clustering and correlation display or highlighting of impacting changes through time. Similarity scoring allows the identification of global patterns in dynamic heterogeneous data. In this paper we demonstrate the utility of the tool on two distinct biological problems of different scales. First, we analyze a medium scale dataset that looks at perturbation effects of the pluripotency regulator Nanog in murine embryonic stem cells. Dynamic cluster analysis suggests alternative indirect links between Nanog and other proteins in the core stem cell network. Moreover, recurrent correlations from the epigenetic to the translational level are identified. Second, we investigate a large scale dataset consisting of genome-wide knockdown screens for human genes essential in the mitotic process. Here, a potential new role for the gene <it>lsm14a </it>in cytokinesis is suggested. We also show how phenotypic patterning allows for extensive comparison and identification of high impact knockdown targets.</p> <p>Conclusions</p> <p>We present a new visualization approach for perturbation screens with multiple phenotypic outcomes. The novel functionality implemented in Arena3D enables effective understanding and comparison of temporal patterns within morphological layers, to help with the system-wide analysis of dynamic processes. Arena3D is available free of charge for academics as a downloadable standalone application from: <url>http://arena3d.org/</url>.</p

Assessment of the Anthelmintic Efficacy of Albendazole in School Children in Seven Countries Where Soil-Transmitted Helminths Are Endemic

Soil-transmitted helminths (roundworms, whipworms and hookworms) infect millions of children in (sub)tropical countries, resulting in malnutrition, growth stunting, intellectual retardation and cognitive deficits. Currently, there is a need to closely monitor anthelmintic drug efficacy and to develop standard operating procedures, as highlighted in a World Health Organization–World Bank meeting on “Monitoring of Drug Efficacy in Large Scale Treatment Programs for Human Helminthiasis” in Washington DC at the end of 2007. Therefore, we have evaluated the efficacy of a commonly used treatment against these parasitic infections in school children in Africa, Asia and South-America using a standardized protocol. In addition, different statistical approaches to analyzing the data were evaluated in order to develop standardized procedures for data analysis. The results demonstrate that the applied treatment was highly efficacious against round- and hookworms, but not against whipworms. However, there was large variation in efficacy across the different trials which warrants further attention. This study also provides new insights into the statistical analysis of efficacy data, which should be considered in future monitoring and evaluation studies of large scale anthelmintic treatment programs. Finally, our findings emphasize the need to update the World Health Organization recommended efficacy threshold for the treatment of STH

Global and local hydrodynamics of bubble columns: effect of gas distributor

Global (level swell) and local (WMS – Wire Mesh Sensor) measurements were made on waters of different purities and air, in a cylindrical laboratory bubble column (2 m tall, 0.127 m dia) using two different gas distributors: a perforated plate (to produce homogeneous flow) and a spider sparger (to produce heterogeneous flow). The level swell method provided the steady space-averaged gas holdup/gas flow rate data. The WMS method provided the actual gas holdups and bubble sizes resolved in time and space at one cross-sectional horizontal plane (1 m above distributor), whose integration yields the timeaveraged data. The following results were obtained: The global and local data agree relatively well; there are distinct differences between the radial profiles and bubble size distributions between the two main flow regimes; the local information identifies why the predictions of published models, which account for the smaller and larger bubbles in the flow, may not perform well; the modelling approaches based on the hindrance and enhancement concepts prove to be suitable for the flow regime identification and description, including the transition range between the homogeneous and heterogeneous flows; based on the hydrodynamics, the specific interfacial area is obtained, together with the mass transfer coefficient

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Fate of plastic waste exposed to sunlight in the aquatic environment : organic pollutants sorption, impact, and transfer

L’accumulation massive de débris plastiques dans le milieu marin est l’une des problématiques environnementales les plus préoccupantes du fait de leur persistance et des connaissances limitées sur leur devenir et leurs impacts. Ce travail a ainsi eu pour but d’étudier le comportement des débris plastiques marins exposés à la lumière solaire et notamment leurs interactions avec les polluants organiques, impacts éco-toxicologiques et transfert vers l’atmosphère. Les phénomènes de sorption et de désorption des Hydrocarbures Aromatiques Polycycliques (HAP) ont été étudiés sur du polyéthylène (PE) sous diverses formes, formulations et degrés de photodégradation. Des variations de la concentration des HAP dans le PE sont observées en fonction des diverses conditions et résultent surtout du degré de cristallinité et d’oxydation des plastiques. Le rôle photosensibilisateur des HAP a été mis en évidence durant la photodégradation de PE non formulé dans l’eau dopée en HAP. L’impact éco-toxicologique du cocktail « PE - photodégradation - HAP » a été évalué sur des organismes marins à différentes échelles trophiques. À l’échelle microbienne, la photodégradation des plastiques favorisent le développement bactérien. À l’échelle des moules, l’impact se traduit par la détection d’un stress oxydatif et d’une neurotoxicité dépendants des organes. Le transfert eau-air des particules plastiques a été évalué en simulant le phénomène d’éclatement de bulles d’air à la surface de l’eau dans des conditions de laboratoire contrôlées. Le transfert s’est avéré possible et dépend de la composition de l’eau, de la taille des bulles et de la taille, type et degré de photodégradation des plastiques.The massive accumulation of plastic debris in the marine environment is one of the most worrying environmental issues due to their persistence and to the limited knowledge of their fate and impacts. Thus, the aim of this work is to study the behavior of marine plastic debris exposed to sunlight and in particular their interactions with organic pollutants, eco-toxicological impacts, and transfer to the atmosphere. The sorption and desorption phenomenon of Polycyclic Aromatic Hydrocarbons (PAHs) has been evaluated on polyethylene (PE) in various forms, formulations, and UV-weathering degree. Variations in the concentration of PAHs in PE, mainly due to the oxidation of plastic and its crystallinity, were observed between various conditions. The role of PAHs as photosensitizers has been proven during the photodegradation of virgin PE in water spiked with PAHs. The eco-toxicological impact of the “PE - photodegradation - PAHs” cocktail was evaluated on marine organisms at different trophic scales. At the microbial level, the photodegradation of plastics increases bacterial development. For mussels, the impact results in the detection of organ-dependent oxidative stress and neurotoxicity. The water-air transfer of plastic particles was evaluated by simulating the bubble bursting phenomenon on the water surface under controlled laboratory conditions. The transfer has been shown to be possible and depends mainly on the water composition, bubble size and the size, and plastic particles size, type, and UV-weathering degree

Characteristics, fate, and impact of marine plastic debris exposed to sunlight: A review

International audienceThe increase of plastic production from the middle of the twentieth century was inevitably followed by an increase in the amount of plastic dumped in the natural environment. There, the plastic debris are exposed to sunlight, temperature, humidity, and physical stress. This can induce photo-oxidative and thermal degradation. This review discusses the mechanism of plastics UV weathering and its characteristics. Comparison of the photodegradation rate and physico-chemical properties are made according to the weathering mode (natural/accelerated) and medium (air/water). Since the photodegradation can lead to plastics fragmentation, this phenomenon is described along with the methodologies used in literature to evaluate the fragmentation. The impact of the photodegraded plastic debris on the marine environment is also presented in term of (i) photodegradation products and stabilizers leakage, (ii) organic pollutants accumulation, transfer, and leakage, and (iii) toxicity on marine organisms

Experimental evidence of plastic particles transfer at the water-air interface through bubble bursting

International audiencePlastic debris in the marine environment are the subject of an extensive literature. According to studies dedicated to the determination of plastic litter abundance and to the characterisation of degradation and fragmentation processes, models were used to estimate the global plastic debris abundance and to simulate their transfer and distribution. Despite these efforts, there is still missing plastic in the models used as areas exist where plastic abundance is less than that estimated. In parallel, microplastics presence in the atmosphere and in remote areas was confirmed suggesting long range atmospheric transport. Potentially addressing both these issues, recent literature suggests that microplastics (MPs) and nanoplastics (NPs) can be transferred from the marine environment to the atmosphere via the bursting of air bubbles at the sea surface. Nevertheless, to date there is no direct evidence of this transfer. In this study, we evaluate plastic particles transfer as a function of MPs/NPs characteristics and water composition by simulating the bubble bursting phenomenon in a laboratory reactor. Size distribution of transferred particles were recorded, and their plastic nature was confirmed using electron microscopy. Results show that under tested conditions, the transfer is possible but limited to particles smaller than 1 μm. The influence of the presence of proxies of components of the sea surface microlayer in the water was evaluated showing a higher particle transfer rate in the presence of a surfactant (sodium dodecyl sulfate) and no significant effect of polysaccharides (xanthan gum and dextran). The surface state of the particles can alter their behaviour in the aqueous phase and thus their transfer to the atmosphere. The effect of bubble size was also evaluated showing a higher transfer rate with the smaller bubble size. In addition, experiments performed with grounded polyethylene (PE) samples showed higher transfer for UV-aged PE than for pristine PE