Objective: To develop a prediction model to predict surgical re-intervention within two years after endometrial ablation (EA) by using a random forest technique (RF). The performance of the developed prediction model was then compared with a previously published multivariate logistic regression model (LR) (1). Design: Retrospective cohort study. Setting: Data from two non-university teaching hospitals in the Netherlands were used. Population: 446 pre-menopausal women who have had an EA for heavy menstrual bleeding between January 2004 and April 2013. Methods: The RF model was trained in MATLAB (2018b) using the TreeBagger function in the Statistics and Machine Learning Toolbox. Main outcome measures: The performance of the two models was compared using the area under the Receiving Operating Characteristic (ROC) curve (AUROC). Measurements and Main Results: The LR model had an AUC of 0.71 (95% CI 0.64-0.78). The RF model had an AUC of 0.63 (95% CI 0.54-0.71). and an AUC of 0.65 (95% CI 0.56-0.74) after hyperparameter optimization. Conclusion: The RF model is not superior compared to the LR model in predicting the outcome of surgical re-intervention within two years after EA. Machine learning techniques are gaining popularity in development of clinical prediction tools, but they are not necessarily superior to traditional statistical logistic regression techniques. The performance of a model is influenced by the sample size and the number of features, hyperparameter tuning and the linearity of associations. Both techniques should be considered when developing a prediction model.

The structure of N-methylacetamide and N,N-dimethylacetamide dimers and hydrogen-bonded complexes of N-methylacetamide and N,N-dimethylacetamide with water molecules (1-3 molecules in the complex) has been studied by the quantum chemical method based on the density functional theory (DFT) approximation using hybrid Becke, three-parameter, Lee-Yang-Parr (B3LYP) functional and gradient-corrected correlation functional of Perdew, Burke and Ernzerhof (PBE), D3 version of Grimme dispersion correction and augmented correlation-consistent polarized valence-only triple-zeta (aug-CC-pVTZ) basis set. The geometrical parameters of hydrogen bonds, binding energies, vibrational bands have been calculated and the Natural Bond Orbital (NBO), quantum theory of atoms in molecules (QTAIM) analyses have been carried out.

High levels of phenotypic variation in resistance appears to be nearly ubiquitous across natural host populations. To date, the molecular processes associated with this variation in nature are poorly known, although theory predicts resistance to evolve at specific loci in response to pathogen -imposed selection. Nucleotide-binding leucine-rich repeat (NLR) genes play an important role in pathogen recognition, downstream defense responses and defense signaling. Exploring the depth of NLR natural variation has the potential to increase our understanding of how NLR diversity is generated and maintained, and how to manage disease resistance. Here, we sequenced the transcriptomes of five different Plantago lanceolata genotypes in response to inoculation by the same strain of obligate fungal pathogen Podosphaera plantaginis. A de novo transcriptome assembly of RNA-sequencing data yielded 24332 gene models with N50 value of 1329 base pairs and gene space completeness of 66.5%, suggesting a high-quality assembly. The gene expression data showed highly varying responses, with each plant genotype having a unique gene expression profile in response to the pathogen, regardless of the resulting resistance phenotype. We discovered a diverse NLR repertoire in P. lanceolata which is consistent with high phenotypic resistance diversity and high genetic diversity of the species. We find evidence of selection generating diversity at some of the NLR loci. Jointly, our results demonstrate that phenotypic resistance diversity results from a crosstalk between different defense mechanisms. In conclusion, characterizing the architecture of resistance in natural host populations may shed unprecedented light on the potential of evolution to generate variation.

At the catchment scales, the use of coupled, physically based and spatially explicit modelling of hydrological processes continue to be expensive due to the high computational costs and the demand for the necessary meteorological input data. As such, physically based models are still rarely used in operational rainfall–runoff forecasting. In addition, for most regions, the required parameterization datasets for the physical models, for example the 3D information on the physical characteristics of the sub-surface, are not available. For operational reasons therefore only simplified physical and conceptual models are routinely used. To improve on the physical and conceptual models, data-based mechanistic modelling concepts or fully data-driven approaches including regression, fuzzy-based or artificial neural networks (ANNs) have been developed and explored. This study evaluates the performance of long short-term memory (LSTM) recurrent neural networks (RNN) and the wavelet neural networks (WNN) for the prediction of rainfall and runoff in data scarce basins. Both models were trained and validated using 31-years (1979-2009) of observed data from three (3) discharge stations, ten (10) rainfall stations with corresponding satellite-derived meteorological data comprising of wind velocity, relative humidity, average temperature and solar radiation. With four (4) optimal hidden layers comprising of thirty (30) neurons each, the best results for the runoff prediction using LSTM-RNN and WNN models were determined with respective R2 of 0.8967 and 0.8820, with rainfall as the most significant predicator variable. For rainfall prediction, the LSTM-RNN outperformed WNN by 11% as measured in terms of R2 and through spatial distribution comparison with observed precipitation, showing that the integration of satellite-observed meteorological data, in the prediction of rainfall and runoff yields good results.

The effects of HCl rotational excited states on the stereodynamics of the Ca+HCl reaction are explored based on quasi-classical trajectory (QCT) theory with potential energy surface (PES) [Verbockhave et al., J. Chem. Phys. 2005,122,204307]. Vibrational level v=0 and rotational level j=0-3 are considered. The polarization-dependent generalized differential cross sections (PDDCSs) and alignments of the product rotational angular momentum are used to demonstrate the stereodynamics effects. The rotational quantum number has a considerable influence on the distribution of vector correlation, including alignment, orientation, and PDDCSs. The product molecules are strongly forward and backward scattering and weakly sideway scattering because the reactant molecule HCl is in the rotational ground state and the lower rotational excited states. Strongly forward scattering is observed while the reactant is in high rotational excited states.

Niche partitioning reduces competition between species and facilitates coexistence. However, species can coexist within the same niche if they have sufficiently similar fitness. Here, we study the interplay between competition and fitness equivalence in diverse large mammal herbivore communities in the framework of modern coexistence theory. We used stable isotope analysis to quantify niche overlaps and compared them to similarities in species’ intrinsic growth rates. We then combined these data with long-term census data to parameterize multispecies models of population dynamics. Isotopic niche partitioning was clumped, with less overlap between, and more overlap within, feeding guilds. This partitioning was in excess of what is mathematically necessary to overcome fitness differences over a wide range of body sizes (~40 to 600 kg). Although partitioning increases population growth rates, coexistence in mammal herbivore communities is maintained primarily by life history traits that ensure some level of fitness equivalence among species.

Letter to the Editor, BJOG Exchange

References1. Ravi, K.; Gunawardana, S.; Ravi, K.; Abeywickrema, M.; Davies, M.; Tough, E. et al. Why stillbirth deserves a place on the medical school curriculum: Stillbirth-related teaching in UK medical schools. BJOG. 2020;127(3):414.2. Frøen, J. E.; Heazell, A.E P.; Flenady, V.; de Bernis, L.; Kinney, M. V.; Blencowe, H. et al. The Lancet Ending Preventable Stillbirths Study Group. Ending preventable stillbirths: an executive summary for The Lancet’s series. Lancet [Internet]. 2016 18 May 2019. Available from: https://www.thelancet.com/pb/assets/raw/Lancet/stories/series/stillbirths2016-exec-summ.pdf.3. UK Foundation Programme Office. F2 Career Destinations Report. 2018.4. Burden, C.; Bradley, S.; Storey, C.; Ellis, A.; Heazell, A.E.P.; Downe, S. et al. From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth. BMC Pregnancy Childbirth. 2016;16:9.—————————————————————————————————————————Funding Support: No specific funding received.—————————————————————————————————————————Statement of Contribution to Authorship: E.C. and D.S. conceived the idea for the Commentary. E.C. performed the literature review and wrote the initial version of the manuscript. D.S. supervised the writing of the manuscript and provided critical feedback prior to submission of the final version.—————————————————————————————————————————Disclosure of Interests: D.S. is an Executive Scientific Editor for BJOG. Otherwise the authors declare that they have no known competing interests or personal relationships that could have influenced the work reported in this paper.—————————————————————————————————————————

A document by Babylakshmi Muthusamy. Click on the document to view its contents.

Objective: To investigate the mediation effect of glucose level on the linking between maternal age and offspring birthweight. Design: Cohort study Setting: Single tertiary center Population: Women who participated in the National Free Preconception Health Examination Project from January 2015 to September 2017 in Dongguan city, China. Methods: A causal mediation analysis was applied to test the potential mediation effect of the glucose level on the association between maternal age and offspring birthweight. Main Outcome Measure: Offspring weight, macorosmia Results: Of 12 044 women with singleton birth were included. The mean birthweight was 3163.12 ± 417.20 g, the frequency of macrosomia was 1.9%, and 1.8% women were in a hyperglycemic state. Mothers aged 30 years and over were significantly more likely to have preconception hyperglycemia [OR (95% CI): 1.82 (1.31, 2.52)]. Both maternal age and preconception glucose level had a significant positive linear association with macrosomia after adjusted potential confounding factors [OR (95% CI): 1.66 (1.22, 2.26), 1.30 (1.14, 1.47), respectively]. The mediation analysis showed that the presence of preconception glucose level mediated significantly 8% [95% CI: 4% to 16%] of the total influence of maternal age on offspring birthweight. Additionally, the mediated effect was increased among women with a history of adverse pregnancy by mediating 18%. Conclusion: The preconception glucose level mediated the association of advanced maternal age with offspring birthweight. It suggested that the importance of preconception glycemic monitoring and control among older mothers to reduce the risk of adverse pregnancy outcome.

Microbial biomass (MB) production and turnover strongly affect soil organic carbon (SOC) accumulation. Microbial carbon use efficiency (CUE) and MB turnover in paddy soil were determined using a novel substrate-independent H218O labeling approach and the effect of long-term fertilization with mineral (NPK) or combined (NPK+OM (manure)) amendments in 0-10, 10-20, and 20-30 cm depths were investigated. Long-term fertilization increased microbial C uptake, CUE, and growth rates, and all indexes were the highest in the NPK+OM treatment. The CUE ranged between 0.07 and 0.23 and showed variable behavior with depth: it reduced in the control treatment, indicating that more C was allocated to energy production than biomass growth, and increased in fertilized soils, showing the shift of C usage for biomass growth. The highest CUE was observed at 20-30 cm in NPK and NPK+OM and indicated that microorganisms overcome the nutrient deficiency in deep soil layers by keeping high C uptake rates at a constant CUE. MBC turnover was more rapid in NPK (10-70 d) and NPK+OM (40-65 d) compared to control (80 d) and intensified with the depth. These findings highlight that under long-term fertilization MB turnover can be controlled by CUE. These shifts in the strategies of microorganisms functioning can explain the accumulation of SOC in heavily fertilized paddy soils.

Excessive salts in soil inhibit enzyme activity, decrease microbial growth and constrain biochemical functioning, which could be alleviated by soil management and fertilization. However, the effect of consecutive chemical fertilizer on soil bacterial community structure under saline environment is poorly understood. Here, a field randomized block design under four nitrogen fertilization rates (0, 150, 300, and 450 kg N hm-2 y-1) was conducted on coastal salt-affected Fluvo-aquic soil. Effect of nitrogen fertilization rates on soil properties and bacterial community was characterized using Illumina Miseq sequencing for 16S rRNA gene. Results indicated that consecutive chemical N fertilization accelerated the improvement of soil chemical and microbial properties under the paddy rice - winter wheat rotation. Soil bacterial community well responded to the nitrogen fertilization and community richness and diversity increased with the nitrogen rates. Predominant bacterial phyla belonged to Proteobacteria, Chloroflexi, Acidobacteria, Actinobacteria and Planctomycetes, whereas Deltaproteobacteria, Anaerolineae, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Actinobacteria and Planctomycetia were dominant bacterial classes. Increasing nitrogen fertilization resulted in an elevation in the relative abundance of classes Alphaproteobacteria, Gammaproteobacteria, Planctomycetia and Nitrospira, and a decline in Anaerolineae, Acidobacteria_Gp6, Cytophagia, Bacilli and Acidobacteria_Gp10. Clear separations in the bacterial communities at class level were observed under different nitrogen fertilization rates. Community structure of classes Alphaproteobacteria, Planctomycetia and Nitrospira was significantly influenced by potential nitrification rate (PNR), and community structure of class Actinobacteria was significantly influenced by carbon mineralization rate (CMR). The results demonstrated that nitrogen fertilization improved nutrients and metabolic activities to more suitable bacterial microhabitats for saline soil.

Even though friction stir welding (FSW) has been shown to produce high performing butt-joints, stress concentration at the weld edges in overlap FSW significantly reduces the performance of these joints. By combining FSW and adhesive bonding into a friction stir (FS) weld-bonding, joint mechanical performance is greatly improved. Quasi-static and fatigue strength of the proposed FS weld-bonding joints was assessed and benchmarked against overlap FSW and adhesive bonding. The characterization of the structural adhesive is also presented, including differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), as well as mechanical characterization with curing temperature. A small process parameter study was made to select proper FSW parameters for AA6082-T6 overlap FSW and FS weld-bonded joints. The adhesive degradation temperature (357ºC) was found to be higher than reported temperatures in the adhesive during welding of FS weld-bonding joints. Higher curing temperatures were found to lead to increased strength while decreasing ductility of the adhesive. The addition of adhesive bonding to the overlap FSW to produce FS weld-bonding resulted in a significant increase in quasi-static and fatigue strength, achieving 79.9% of the fatigue strength of adhesive bonded joints at 106 cycles, while FSW had 41.6%.

Mini-commentary on BJOG-19-1615.R1: Pregnancy outcomes in women with primary biliary cholangitis and primary sclerosing cholangitis

A document by Mahendra Kashyap. Click on the document to view its contents.

Background and Purpose: Prunus amygdalus (PA) is a popular invasive seed utilized in the management of diabetes in Jammu and Kashmir, India. The current study scrutinizes the antihyperglycemic effect of PA on Streptozotocin (STZ) induced diabetic rats. Experimental approach: BBD was performed to determine the effect of PA powder on methanol, extraction time and extraction temperature on DPPH and ABTS free radical scavenging activity of decoction. Oral glucose tolerance test (OGTT) executed for the estimation of glucose utilization by PA extract. Type II diabetes mellitus was initiated by single intraperitoneal injection of STZ. The Blood Glucose Level (BGL) and body weight were estimated at regular interval of time. Different biochemical parameters; hepatic parameters; antioxidant parameters and lipid parameters were estimated followed by histopathological observation. of pancreas Key Results: The variation observed were DPPH antiradical scavenging activity 40.0-90.0% and ABTS antiradical scavenging activity 34-82%, respectively. OGTT study, PA treatment significantly (P<0.001) down-regulated the BGL level 170, 142.66 and 100.36 mg/dL at 50, 100 and 200 mg/kg, respectively. PA significantly (P<0.001) altered the biochemical, hepatic and antioxidant parameters in a dose-dependent manner. Further alteration of antioxidant parameters, hepatic and renal parameters were also observed. Histopathological examination demonstrated the increased mass of β-cells in the pancreas. Conclusions & Implications: Consequently, we can say that response surface methodologies successfully carry out the extraction of Prunus amygdalus with the highest antioxidant effect and PA treatment would be helpful in the preclusion of diabetes and its complications.

Rational, aims and objectives: This study aimed to assess knowledge, attitude and practice (KAP) of using insulin pen in diabetes and determine the related factors to the KAP, adverse drug reactions (ADRs) and glycemic control status. Methods: In our descriptive study, 148 patients with diabetes were interviewed by 16-item questions on knowledge and 8 questions on attitude, and were asked to present the insulin pen injection technique with a sample insulin pen. Results: Proportions of patient having a good knowledge, positive attitude, and good practice were 45.9%, 78.4%, and 44.6%, respectively. The three most incorrect steps were skipping to prime pen needle (90.9%), not removing the used needle from the pen after using (87.8), and not holding for specific count time before withdrawal of pen needle from skin (50.7%). Patients having duration of insulin one year or more had better knowledge (p=0.025), more positive attitude (p=0.017), and better practice of insulin (p=0.042). Patients using insulin combined with oral diabetic medications or having history of using insulin vials had more positive attitude of insulin role (0.038). Frequency of having good knowledge was statistically significantly higher in participants who received counseling from health professionals previously (p=0.001). The study also found a positive correlation between good knowledge of patients and good practical skills (p<0.001). Patients with poor practice of insulin were more likely to have ADRs at the injection sites (p = 0.013). The worse knowledge of patients was significant related to the higher risk of hypoglycemia (p=0.001). KAP levels did not correlate with glycemic control status. Conclusions: Positive attitude in patients was recorded at a significant rate; however, knowledge and practice needs improvement. This study was helpful to shape the patient education and target specific patients for education.

The potassium channel Kv1.3 is an important pharmacological target and the Kaliotoxin-type toxins (α-KTX-3 family) are its specific blockers. Here, we study the binding process of two kinds of Kaliotoxin-type toxins:BmKTX and its mutant (BmKTX-D33H) toward to Kv1.3 channel using MD simulation and umbrella sampling simulation, respectively. The calculated binding free energies are -27 kcal/mol and -34 kcal/mol for BmKTX and BmKTX-D33H, respectively, which are consistent with experimental results. The further analysis indicate that the characteristic of electrostatic potential of the α-KTX-3 have important effect on their binding modes with Kv1.3 channel; the residue 33 in BmKTX and BmKTX-D33H plays a key role in determine their binding orientations toward to Kv1.3 channel; when residue 33( or 34) has negative electrostatic potential, the anti-parallel β-sheet domain of α-KTX-3 toxin peptide will keep away from the filter region of Kv1.3 channel, as BmKTX; when residue 33(or 34) has positive electrostatic potential, the anti-parallel β-sheet domain of α-KTX-3 toxin peptide will interact with the filter region of Kv1.3 channel, as BmKTX-D33H. Above all, electrostatic potential differences on toxin surfaces and correlations motions within the toxins will determine the toxin-potassium channel interaction model. In addition, the hydrogen bond interaction is the pivotal factor for the Kv1.3- Kaliotoxin association. Understanding the binding mechanism of toxin–potassium channel will facilitate the rational development of new toxin analogue.

The selection of a powerful measure to characterize and describe the inputs and outputs of mountainous rivers is of prime importance. Information and complexity metrics have the ability to reveal invaluable information about the hydrological processes that occur within a system. In this work, the hourly streamflow records obtained from five gauging stations for a mountainous river were analyzed to quantify the different patterns and characterize system states at low and high frequencies using increasing aggregation lengths. In addition, we proposed a new extension for the information and complexity theory to be customized for flood assessment. Moreover, we clarified how a pattern (i.e. a word length) by means of information and complexity metrics can be suitably defined. Regarding the low frequency analyses, the information and complexity metrics showed that river discharge has two scaling regimes one of them may describe the river memory characteristics. Furthermore, for high frequency findings, an additional scaling regime that occurs within hourly scales captured by streamflow data obtained by a novel hydroacoustic system, which is one of the novel aspects of our work. Additionally, the power spectral density results match with our findings. This work reveals the performance of information and complexity metrics to be customized for analyzing streamflow patterns at different temporal scales.

Traditional Chinese Medicines (TCMs) is used in China as part of the treatment for non-small-cell lung cancer (NSCLC) and often includes prescription in combination with conventional therapies based on syndrome differentiation. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) represent the first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). In China, EGFR-TKIs may be combined with TCMs with the aim of reducing the side effects and/or augmenting the efficacy of the EGFR-TKIs. However, the relationship between TCMs and EGFR-TKIs remain unclear. So, this meta-review evaluates the clinical evidence of TCMs combined with EGFR-TKIs in the treatment of NSCLC. Seven electronic databases were searched for randomized controlled trials of EGFR-TKI combined with TCMs compared to the EGFR-TKIs alone. Fifty-seven randomized controlled trials were involved in this study, and all the data were analyzed by Stata software (version 12.0). This study suggested that the objective response rate (ORR) of the group with TCMs combined with EGFR-TKIs-based regimens was higher than the group of EGFR-TKIs alone (RR 1.39, 95% CI [1.29, 1.50]). Further sensitivity analysis of specific plant-based TCMs showed that Huangqi, Baishu, Fuling, Gancao, Maidong, Baihuashecao, Shashen, Renshen and Dangshen, had significantly higher contributions to the results. Therefore, TCMs may have the potential to improve the efficacy of EGFR-TKIs for NSCLC.

Interrogation of chromatin modifications, such as DNA methylation, has potential to improve forecasting and conservation of marine ecosystems. The standard method for assaying DNA methylation (Whole Genome Bisulfite Sequencing), however, is too costly to apply at the scales required for ecological research. Here we evaluate different methods for measuring DNA methylation for ecological epigenetics. We compare Whole Genome Bisulfite Sequencing (WGBS) with Methylated CpG Binding Domain Sequencing (MBD-seq), and a modified version of MethylRAD we term methylation-dependent Restriction site-Associated DNA sequencing (mdRAD). We evaluate these three assays in measuring variation in methylation across the genome, between genotypes, and between polyp types in the reef-building coral Acropora millepora. We find that all three assays measure absolute methylation levels similarly, with tight correlations for methylation of gene bodies (gbM), as well as exons and 1Kb windows. Correlations for differential gbM between genotypes were weaker, but still concurrent across assays. We detected little to no reproducible differences in gbM between polyp types. We conclude that MBD-seq and mdRAD are reliable cost-effective alternatives to WGBS. Moreover, the considerably lower sequencing effort required for mdRAD to produce comparable methylation estimates makes it particularly useful for ecological epigenetics.

Phylogenetic diversity of symbiotic bacteria in sucking lice suggests that lice have experienced a complex history of symbiont acquisition, loss, and replacement during their evolution. By combining metagenomics and amplicon screening across several populations of two louse genera (Polyplax and Hoplopleura) we describe a novel louse symbiont lineage related to Neisseria and Snodgrassella, and show its independent origin within dynamic lice microbiomes. While the genomes of these symbionts are highly similar in both lice genera, their respective distributions and status within lice microbiomes indicate that they have different functions and history. In Hoplopleura acanthopus, the Neisseria-related bacterium is a dominant obligate symbiont universally present across several host’s populations, and seems to be replacing a presumably older and more degenerated obligate symbiont. In contrast, the Polyplax microbiomes are dominated by the obligate symbiont Legionella polyplacis, with the Neisseria-related bacterium co-occurring only in some samples and with much lower abundance.

1. Global warming is rapidly emerging as a universal threat that could alter the distribution of many animal species and change their morphology, physiology, behavior and life history. The heat dissipation limitation (HDL) hypothesis proposes that females’ reproductive performance is limited by their capacity to dissipate heat. Although exposure to wind is known to increase heat exchange, its effect on reproductive performance is unknown. 2. In this study, the effect of simulated wind on the energy budget and milk energy output of female striped hamsters (Cricetulus barabensis) was measured under cool (21°C) and hot (32.5°C) ambient temperatures and the preference of hamsters for windy conditions in lactating females was tested both in the laboratory and the wild. 3. Females lactating at 32.5°C significantly decreased their energy intake and milk output, and raised lighter offspring than those lactating at 21°C. Exposure to wind significantly increased both energy intake during lactation and heat loss at both temperatures. Females lactating at 32.5°C considerably increased their reproductive output when exposed to wind. Moreover, females kept at an ambient temperature of 21°C preferred sheltered conditions whereas those kept at 32.5°C preferred exposure to simulated wind. We captured significantly more lactating female hamsters on windy days in summer and on calm days in spring. Wrapping a glass vessel in the fresh pelt of a striped hamster significantly reduced the rate of both water loss and cooling. 4. These findings support the HDL hypothesis; high ambient temperatures do appear to limit the energy intake and reproductive output of lactating hamsters. Small mammals lactating under hot conditions may be able to utilize the cooling properties of wind to increase their energy intake and milk production, and thereby their reproductive output and fitness.

An extended computational approach has been utilized to explore the reactions of acids with carbonyl oxide, also known as Criegee intermediate (CI). The reactions were explored inside water cluster containing 50 water molecules. All possibilities of product formation were considered. Among the considered acids, the rate of 1,4-insertion follows the order - HCOO < HCl < HNO3. The most stable products of the reactions between the considered acids and CI have been identified.