HOME: A histogram based machine learning approach for effective identification of differentially methylated regions

Background The development of whole genome bisulfite sequencing has made it possible to identify methylation differences at single base resolution throughout an entire genome. However, a persistent challenge in DNA methylome analysis is the accurate identification of differentially methylated regions (DMRs) between samples. Sensitive and specific identification of DMRs among different conditions requires accurate and efficient algorithms, and while various tools have been developed to tackle this problem, they frequently suffer from inaccurate DMR boundary identification and high false positive rate. Results We present a novel Histogram Of MEthylation (HOME) based method that takes into account the inherent difference in the distribution of methylation levels between DMRs and non-DMRs to discriminate between the two using a Support Vector Machine. We show that generated features used by HOME are dataset-independent such that a classifier trained on, for example, a mouse methylome training set of regions of differentially accessible chromatin, can be applied to any other organism’s dataset and identify accurate DMRs. We demonstrate that DMRs identified by HOME exhibit higher association with biologically relevant genes, processes, and regulatory events compared to the existing methods. Moreover, HOME provides additional functionalities lacking in most of the current DMR finders such as DMR identification in non-CG context and time series analysis. HOME is freely available at https://github.com/ListerLab/HOME . Conclusion HOME produces more accurate DMRs than the current state-of-the-art methods on both simulated and biological datasets. The broad applicability of HOME to identify accurate DMRs in genomic data from any organism will have a significant impact upon expanding our knowledge of how DNA methylation dynamics affect cell development and differentiation.This work was supported by the Australian Research Council (ARC) Centre of Excellence program in Plant Energy Biology (CE140100008). RL was supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship, ARC Future Fellowship (FT120100862), and Howard Hughes Medical Institute International Research Scholarship (RL

The effects of explicit versus parameterized convection on the MJO in a large-domain high-resolution tropical case study. Part II: Processes leading to differences in MJO development

High-resolution simulations over a large tropical domain (∼20◦S–20◦N and 42◦E–180◦E) using both explicit and parameterized convection are analyzed and compared during a 10-day case study of an active Madden-Julian Oscillation (MJO) event. In Part II, the moisture budgets and moist entropy budgets are analyzed. Vertical subgrid diabatic heating profiles and vertical velocity profiles are also compared; these are related to the horizontal and vertical advective components of the moist entropy budget which contribute to gross moist stability, GMS, and normalized GMS (NGMS). The 4-km model with explicit convection and good MJO performance has a vertical heating structure that increases with height in the lower troposphere in regions of strong convection (like observations), whereas the 12-km model with parameterized convection and a poor MJO does not show this relationship. The 4-km explicit convection model also has a more top-heavy heating profile for the troposphere as a whole near and to the west of the active MJO-related convection, unlike the 12-km parameterized convection model. The dependence of entropy advection components on moisture convergence is fairly weak in all models, and differences between models are not always related to MJO performance, making comparisons to previous work somewhat inconclusive. However, models with relatively good MJO strength and propagation have a slightly larger increase of the vertical advective component with increasing moisture convergence, and their NGMS vertical terms have more variability in time and longitude, with total NGMS that is comparatively larger to the west and smaller to the east

Visual Hints for Tangible Gestures in Augmented Reality

Tangible Augmented Reality (AR) systems imbue physical ob-jects with the ability to act and respond in new ways. In particu-lar, physical objects and gestures made with them gain meaning that does not exist outside the tangible AR environment. The existence of this new set of possible actions and outcomes is not always apparent, making it necessary to learn new movements or gestures. Addressing this opportunity, we present visual hints, which are graphical representations in AR of potential actions and their consequences in the augmented physical world. Visual hints enable discovery, learning, and completion of gestures and ma-nipulation in tangible AR. Here, we discuss our investigation of a variety of representations of visual hints and methods for activat-ing them. We then describe a specific implementation that sup-ports gestures developed for a tangible AR user interface to an electronic field guide for botanists, and present results from a pilot study

The value and significance of corporate community relations: an Italian SME perspective

Purpose – This paper investigates the link between community of place and small and medium-sized enterprises (SMEs) in Lombard industrial districts in Italy. Design/methodology/approach – A brief literature review of international authors from the stakeholder approach and Corporate Community Relations field is presented. This paper refers to a survey of Lombard industrial districts conducted by ALTIS. The data was collected via a telephone survey from 834 firms. Findings – The main finding is that managing Corporate Community Relations (CCR) is of major importance for company success. The results of the survey show that there are some tools and actions that Italian industrial district SMEs uses to interact with their particular communities of place to develop effective and coherent relationships with their stakeholder groups. Moreover, although the survey shows that though SMEs do implement different CCR activities, they are not able to communicate these effectively through systematic communication strategies. However, the narrow sample includes only a sample of some Lombard districts. Nonetheless, the findings indicate that effective CCR seems to confer competitive advantage based on stakeholder responses and rewards sought. Research limitations/implications – The framework could assist in supporting CCR developments between industrial districts as various players would know how to improve CCR activities. One further suggestion is that University and Research Centres could have a role to play in creating and communicating codified knowledge concerning community relations in industrial districts, while other public players still have to develop specific tasks in improving infrastructures. Originality/value – This study is in line with the main focus of CCR, which is in striving to meet stakeholder and societal needs. However, industrial district SMEs have to learn how to communicate their CCR activities from the examples set by large Italian companies. The paper links the notion of CCR with tools and actions to develop meaningful relationships with both community of place and interest. Moreover, considering the survey results, a new framework for local player roles is proposed

Patient and economic impact of implementing a paediatric sepsis pathway in emergency departments in Queensland, Australia.

We examined systems-level costs before and after the implementation of an emergency department paediatric sepsis screening, recognition and treatment pathway. Aggregated hospital admissions for all children aged < 18y with a diagnosis code of sepsis upon admission in Queensland, Australia were compared for 16 participating and 32 non-participating hospitals before and after pathway implementation. Monte Carlo simulation was used to generate uncertainty intervals. Policy impacts were estimated using difference-in-difference analysis comparing observed and expected results. We compared 1055 patient episodes before (77.6% in-pathway) and 1504 after (80.5% in-pathway) implementation. Reductions were likely for non-intensive length of stay (- 20.8 h [- 36.1, - 8.0]) but not intensive care (-9.4 h [- 24.4, 5.0]). Non-pathway utilisation was likely unchanged for interhospital transfers (+ 3.2% [- 5.0%, 11.4%]), non-intensive (- 4.5 h [- 19.0, 9.8]) and intensive (+ 7.7 h, [- 20.9, 37.7]) care length of stay. After difference-in-difference adjustment, estimated savings were 596 [277, 942] non-intensive and 172 [148, 222] intensive care days. The program was cost-saving in 63.4% of simulations, with a mean value of $97,019 [-$857,273, $1,654,925] over 24 months. A paediatric sepsis pathway in Queensland emergency departments was associated with potential reductions in hospital utilisation and costs

The representation of the West-African Monsoon vertical cloud structure in the Met Office Unified Model: an evaluation with CloudSat

Weather and climate model simulations of the West African Monsoon (WAM) have generally poor representation of the rainfall distribution and monsoon circulation because key processes, such as clouds and convection, are poorly characterized. The vertical distribution of cloud and precipitation during the WAM are evaluated in Met Office Unified Model simulations against CloudSat observations. Simulations were run at 40-km and 12-km horizontal grid length using a convection parameterization scheme and at 12-km, 4-km, and 1.5-km grid length with the convection scheme effectively switched off, to study the impact of model resolution and convection parameterization scheme on the organisation of tropical convection. Radar reflectivity is forward-modelled from the model cloud fields using the CloudSat simulator to present a like-with-like comparison with the CloudSat radar observations. The representation of cloud and precipitation at 12-km horizontal grid length improves dramatically when the convection parameterization is switched off, primarily because of a reduction in daytime (moist) convection. Further improvement is obtained when reducing model grid length to 4 km or 1.5 km, especially in the representation of thin anvil and mid-level cloud, but three issues remain in all model configurations. Firstly, all simulations underestimate the fraction of anvils with cloud top height above 12 km, which can be attributed to too low ice water contents in the model compared to satellite retrievals. Secondly, the model consistently detrains mid-level cloud too close to the freezing level, compared to higher altitudes in CloudSat observations. Finally, there is too much low-level cloud cover in all simulations and this bias was not improved when adjusting the rainfall parameters in the microphysics scheme. To improve model simulations of the WAM, more detailed and in-situ observations of the dynamics and microphysics targeting these non-precipitating cloud types are required

Aid Allocation of the Emerging Central and Eastern European Donors

The paper examines the main characteristics of the (re)emerging foreign aid policies of the Visegrád countries (the Czech Republic, Hungary, Poland, Slovakia), concentrating on the allocation of their aid resources. We adopt an econometric approach, similar to the ones used in the literature for analyzing the aid allocation of the OECD DAC donors. Using this approach, we examine the various factors that influence aid allocation of the Visegrád countries, using data for the years between 2001 and 2008. Our most important conclusion is that the amount of aid a partner county gets from the four emerging donors is not influenced by the level of poverty or the previous performance (measured by the level of economic growth or the quality of institutions) of the recipients. The main determining factor seems to be geographic proximity, as countries in the Western-Balkans and the Post-Soviet region receive much more aid from the Visegrád countries than other recipients. Historical ties (pre-1989 development relations) and international obligations in the case of Afghanistan and Iraq are also found to be significant explanatory factors. This allocation is in line with the foreign political and economic interests of these new donors. While there are clear similarities between the four donors, the paper also identifies some individual country characteristics

Sex-differences in oral anticoagulation therapy in patients hospitalized with atrial fibrillation:a nationwide cohort study

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67–0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66–0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90–0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men

On the lifetime of the 2+ state in 10C

The lifetime of the J=2+ state in 10C was measured using the Doppler Shift Attenuation Method following the inverse kinematics p(10B,n)10C reaction at 95 MeV. The 2+ state, at 3354 keV, has tau = 219\pm(7)stat \pm(10)sys fs corresponding to a B(E2) # of 8.8(3) e2fm4. This measurement,combined with that recently determined for 10Be (9.2(3) e2fm4), provides a unique challenge to abinitio calculations, testing the structure of these states, including the isospin symmetry of the wave functions. Quantum Monte Carlo calculations using realistic two- and three-nucleon Hamiltonians that reproduce the 10Be B(E2) value generally predict a larger 10C B(E2) probability but with considerable sensitivity to the admixture of different spatial symmetry components in the wave functions, and to the three-nucleon potential used.Comment: Experimental and Theoretical Investigatio