bluuebunny/crossref_metadata_2025 huggingface dataset:
Production planning and scheduling problem of continuous parallel lines with demand uncertainty and different production capacities
Authors: Bhosale Kailash Changdeorao , Pawar Padmakar Jagannath
Published: June 2020

Production planning and scheduling problems are highly interdependent as scheduling provides optimum allocation of resources and planning is an optimum utilization of these allocated resources to serve multiple customers. Researchers have solved production planning and scheduling problems by the sequential method. But, in this case, the solution obtained by the production planning problem may not be feasible for scheduling method. Hence, production planning and scheduling problems must be solved simultaneously. Therefore, in this work, a mathematical model is developed to integrate production planning and scheduling problems. The solution to this integrated planning and scheduling problem is attempted by using a discrete artificial bee colony (DABC) algorithm. To speed up the DABC algorithm, a k-means clustering algorithm is used in the initial population generation phase. This k-means clustering algorithm will help to converge the algorithm in lesser time. A real-life case study of a soap manufacturing industry is presented to demonstrate the effectiveness of the proposed approach. An objective function to minimize overall cost, which comprises the processing cost, material cost, utility cost, and changeover cost, is considered. The results obtained by using DABC algorithm are compared with those obtained by CPLEX software. There is a saving of ₹2 23 324 for weeks 1–4 in overall cost compared with the results obtained by using CPLEX software.
The Effects of Population Density on the Incidence of Developmental Deformities in Chemosensory Organs of Tobacco Hornworm Larvae (Lepidoptera: Sphingidae)
Authors: Hanson Frank , Stanwyck Elizabeth , Bohorquez Alexander
Published: June 2020

Cultures of Manduca sexta Johanssen in our laboratory were found to have larvae with missing or deformed mouthparts or antennae. Hypothesizing that these developmental deformities were caused by crowded rearing conditions, we reared larvae in four different population densities and recorded the incidence (% of larvae affected) and types of chemoreceptor deformities. Results showed that the incidence of these deformities was directly proportional to larval population density. Deformities of the maxilla and palp were the most frequent, followed by those of the antenna, epipharynx and maxillary styloconica. Life history traits of larval mass, food consumption, and rate of development were inversely related to larval density for both normal and deformed larvae. We discuss possible causes and mechanisms of these deformities and of changes to life history traits.
A Moving Target—Vancomycin Therapeutic Monitoring
Authors: Burns Alaina N , Goldman Jennifer L
Published: June 2020

Therapeutic drug monitoring (TDM) has been a common practice to optimize efficacy and safety of vancomycin. While vancomycin trough-only TDM has widely been integrated into pediatric clinical practice since 2009, recently updated vancomycin TDM guidelines published in March 2020 recommend area under the curve (AUC) based TDM for vancomycin instead of trough-only TDM. In this review, we discuss the rationale behind the change in TDM recommendations, describe two approaches for calculating vancomycin AUC in clinical practice, and address considerations for integrating vancomycin AUC TDM into pediatric clinical practice. Our primary goal is to provide pediatric clinicians with a resource for implementing vancomycin AUC monitoring into clinical care.
Obesity and ventral hernia in the context of drug addiction and mental instability: a complex scenario successfully treated with preoperative progressive pneumoperitoneum
Authors: Moyón C F Xavier , Molina Gabriel A , Rojas Christian L , Moyón C Miguel A , Tufiño Jorge F , Cárdenas Andrés , Mafla Oscar L , Camino John E , Basantes Ligia Elena , Villacis Marcelo Stalin
Published: June 2020

Surgery in loss of domain hernia can result in high morbidity and mortality. Chronic muscle retraction along with the reduced volume of the peritoneal cavity can lead to potential problems such as abdominal compartment syndrome, ventilatory restriction and an elevated risk of hernia recurrence. This is affected even further by obesity; a high body mass index is strongly associated with poor outcomes after ventral hernia repair. In these individuals, preoperative preparation is vital as it can reduce surgical risks and improve patients’ outcomes. There are many strategies available. Nonetheless, an individualized case approach by a multidisciplinary team is crucial to accurately treat this troublesome pathology. We present the case of a 41-year-old obese patient with a loss of domain ventral hernia. As he had a drug addiction and several psychologic difficulties, a tailored approach was needed to successfully treat the hernia. After preoperative preparation and surgery, the patient underwent full recovery.
Predicting FIR lines from simulated galaxies
Authors: Lupi Alessandro , Pallottini Andrea , Ferrara Andrea , Bovino Stefano , Carniani Stefano , Vallini Livia
Published: June 2020

Far-infrared (FIR) emission lines are a powerful tool to investigate the properties of the interstellar medium, especially in high-redshift galaxies, where ALMA observations have provided unprecedented information. Interpreting such data with state-of-the-art cosmological simulations post-processed with cloudy, has provided insights on the internal structure and gas dynamics of these systems. However, no detailed investigation of the consistency and uncertainties of this kind of analysis has been performed to date. Here, we compare different approaches to estimate FIR line emission from state-of-the-art cosmological simulations, either with cloudy or with on-the-fly non-equilibrium chemistry. We find that [C ii]158μ predictions are robust to the model variations we explored. [O i] emission lines, that typically trace colder and denser gas relative to [C ii]158μ, are instead model dependent, as these lines are strongly affected by the thermodynamic state of the gas and non-equilibrium photoionization effects. For the same reasons, [O i] lines represent an excellent tool to constrain emission models, hence future observations targeting these lines will be crucial.
Time lags of the type-B quasi-periodic oscillation in MAXI J1348−630
Authors: Belloni Tomaso M , Zhang Liang , Kylafis Nikolaos D , Reig Pablo , Altamirano Diego
Published: June 2020

The fast variability observed in the X-ray emission from black hole binaries has a very complex phenomenology, but offers the possibility to investigate directly the properties of the inner accretion flow. In particular, type-B oscillations in the 2–8 Hz range, observed in the soft-intermediate state, have been associated with the emission from a relativistic jet. We present the results of the timing and spectral analysis of a set of observations of the bright transient MAXI J1348−630 made with the NICER (Neutron Star Interior Composition Explorer) telescope. The observations are in the brightest part of the outburst and all feature a strong type-B quasi-periodic oscillation (QPO) at ∼4.5 Hz. We compute the energy dependence of the fractional rms and the phase lags at the QPO frequency, obtaining high signal-to-noise data and sampling for the first time at energies below 2 keV. The fractional rms decreases from more than 10 per cent at 9 keV to 0.6 per cent at 1.5 keV, and is constant below that energy. Taking the 2–3 keV band as reference, photons at all energies show a hard lag, increasing with the distance from the reference band. The behaviour below 2 keV has never been observed before, due to the higher energy bandpass of previous timing instruments. The energy spectrum can be fitted with a standard model for this state, consisting of a thin disc component and a harder power law, plus an emission line between 6 and 7 keV. We discuss the results, concentrating on the phase lags, and show that they can be interpreted within a Comptonization model.
Properties of the circumgalactic medium in cosmic ray-dominated galaxy haloes
Authors: Ji Suoqing , Chan T K , Hummels Cameron B , Hopkins Philip F , Stern Jonathan , Kereš Dušan , Quataert Eliot , Faucher-Giguère Claude-André , Murray Norman
Published: June 2020

We investigate the impact of cosmic rays (CRs) on the circumgalactic medium (CGM) in FIRE-2 simulations, for ultra-faint dwarf through Milky Way (MW)-mass haloes hosting star-forming (SF) galaxies. Our CR treatment includes injection by supernovae, anisotropic streaming and diffusion along magnetic field lines, and collisional and streaming losses, with constant parallel diffusivity $\kappa \sim 3\times 10^{29}\, \mathrm{cm^2\ s^{-1}}$ chosen to match γ-ray observations. With this, CRs become more important at larger halo masses and lower redshifts, and dominate the pressure in the CGM in MW-mass haloes at z ≲ 1–2. The gas in these ‘CR-dominated’ haloes differs significantly from runs without CRs: the gas is primarily cool (a few ${\sim}10^{4}\,$ K), and the cool phase is volume-filling and has a thermal pressure below that needed for virial or local thermal pressure balance. Ionization of the ‘low’ and ‘mid’ ions in this diffuse cool gas is dominated by photoionization, with O vi columns ${\gtrsim}10^{14.5}\, \mathrm{cm^{-2}}$ at distances ${\gtrsim}150\, \mathrm{kpc}$. CR and thermal gas pressure are locally anticorrelated, maintaining total pressure balance, and the CGM gas density profile is determined by the balance of CR pressure gradients and gravity. Neglecting CRs, the same haloes are primarily warm/hot ($T\gtrsim 10^{5}\,$K) with thermal pressure balancing gravity, collisional ionization dominates, O vi columns are lower and Ne viii higher, and the cool phase is confined to dense filaments in local thermal pressure equilibrium with the hot phase.
Constraints on the star formation histories of galaxies in the Local Cosmological Volume
Authors: Kroupa P , Haslbauer M , Banik I , Nagesh S T , Pflamm-Altenburg J
Published: June 2020

The majority of galaxies with current star formation rates (SFRs), $\rm SFR_{\rm o} \ge 10^{-3} \, M_\odot\,yr^{-1}$, in the Local Cosmological Volume, where observations should be reliable, have the property that their observed SFRo is larger than their average SFR. This is in tension with the evolution of galaxies described by delayed-τ models, according to which the opposite would be expected. The tension is apparent in that local galaxies imply the star formation time-scale τ ≈ 6.7 Gyr, much longer than the 3.5–4.5 Gyr obtained using an empirically determined main sequence at several redshifts. Using models where the SFR is a power law in time of the form ∝(t − t1)η for t1 = 1.8 Gyr (with no stars forming prior to t1) implies that η = 0.18 ± 0.03. This suggested near-constancy of a galaxy’s SFR over time raises non-trivial problems for the evolution and formation time of galaxies, but is broadly consistent with the observed decreasing main sequence with increasing age of the Universe.
FETCH: A deep-learning based classifier for fast transient classification
Authors: Agarwal Devansh , Aggarwal Kshitij , Burke-Spolaor Sarah , Lorimer Duncan R , Garver-Daniels Nathaniel
Published: June 2020

With the upcoming commensal surveys for Fast Radio Bursts (FRBs), and their high candidate rate, usage of machine learning algorithms for candidate classification is a necessity. Such algorithms will also play a pivotal role in sending real-time triggers for prompt follow-ups with other instruments. In this paper, we have used the technique of Transfer Learning to train the state-of-the-art deep neural networks for classification of FRB and Radio Frequency Interference (RFI) candidates. These are convolutional neural networks which work on radio frequency-time and dispersion measure-time images as the inputs. We trained these networks using simulated FRBs and real RFI candidates from telescopes at the Green Bank Observatory. We present 11 deep learning models, each with an accuracy and recall above 99.5 per cent on our test data set comprising of real RFI and pulsar candidates. As we demonstrate, these algorithms are telescope and frequency agnostic and are able to detect all FRBs with signal-to-noise ratios above 10 in ASKAP and Parkes data. We also provide an open-source python package fetch (Fast Extragalactic Transient Candidate Hunter) for classification of candidates, using our models. Using fetch, these models can be deployed along with any commensal search pipeline for real-time candidate classification.
A unified view of the sequence and functional organization of the human RNA polymerase II promoter
Authors: Luse Donal S , Parida Mrutyunjaya , Spector Benjamin M , Nilson Kyle A , Price David H
Published: June 2020

To better understand human RNA polymerase II (Pol II) promoters in the context of promoter-proximal pausing and local chromatin organization, 5′ and 3′ ends of nascent capped transcripts and the locations of nearby nucleosomes were accurately identified through sequencing at exceptional depth. High-quality visualization tools revealed a preferred sequence that defines over 177 000 core promoters with strengths varying by >10 000-fold. This sequence signature encompasses and better defines the binding site for TFIID and is surprisingly invariant over a wide range of promoter strength. We identified a sequence motif associated with promoter-proximal pausing and demonstrated that cap methylation only begins once transcripts are about 30 nt long. Mapping also revealed a ∼150 bp periodic downstream sequence element (PDE) following the typical pause location, strongly suggestive of a +1 nucleosome positioning element. A nuclear run-off assay utilizing the unique properties of the DNA fragmentation factor (DFF) coupled with sequencing of DFF protected fragments demonstrated that a +1 nucleosome is present downstream of paused Pol II. Our data more clearly define the human Pol II promoter: a TFIID binding site with built-in downstream information directing ubiquitous promoter-proximal pausing and downstream nucleosome location.
Guillermo del Toro
Authors: Tierney Dolores
Published: June 2020

Guillermo del Toro (b. 1964) is an Oscar-winning Mexican director, screenwriter, producer, novelist, film scholar, curator, and nonfiction writer who works internationally on English-language and Spanish-language projects in Mexico, New Zealand, Spain, and the United States and across a number of different media, including film, television, animation, and novels. Although he has worked in multiple genres, including horror (Mimic (1997), Blade II (2002), Crimson Peak (2015)), action/fantasy (Hellboy (2004), Hellboy II: The Golden Army (2008)), science fiction (Pacific Rim (2013)), and hybrids of these and other genres (The Shape of Water (2017)), he is most known for the gothic sensibility of many of his projects (Cronos (1993), The Devil’s Backbone (2001), Pan’s Labyrinth (2006), Crimson Peak (2015)). Relatedly, Del Toro’s Cronos and his subsequent films, including those he has produced have contributed greatly to the rehabilitation of the horror and fantasy genres from the cultural disreputability they suffered through the 1960s to the early 1990s and also facilitated more horror production in Mexico going forward. In addition to the gothic quality of his work, Del Toro’s auteur status is often traced through the recurring imagery, themes, and monsters that appear across his oeuvre and through the recurring preoccupations with the contiguity of real and fantasy worlds and with ghosts as manifestations of the (historical and political) past. Although Del Toro has made and been involved in the production of some notable franchise films in recent years, directing Blade II, Hellboy, and Hellboy II: The Golden Army, receiving a screenwriting credit for The Hobbit: An Unexpected Journey (2012), The Hobbit: The Desolation of Smaug (2013), and The Hobbit: The Battle of the Five Armies (2014) he has also turned down several opportunities to work on franchise films in the Narnia and Harry Potter series (passing on directing Harry Potter and the Prisoner of Azkaban but suggesting his compatriot Alfonso Cuarón for the job instead) and leaving the production of The Hobbit films after work on the scripts. He’s also received writing credit on Trox Nixey’s Don’t Be Afraid of the Dark (2010).
Modernism and Postmodernism in Chinese Literature
Authors: Storm Carsten , Lin Pei-yin
Published: June 2020

Modernism and postmodernism are highly contested terms, both in theory and in academic practice. Both are understood here primarily as a mixture of literary styles and agendas, of times and/or areas of flourishment, and of canon (i.e., a selection of typical texts and authors through journals, criticism, or the academy). While the advent of modernity in China can be traced back to the second half of the 19th century, modernism as such does not gain momentum in Chinese literary discourses until the second decade of the 20th century and was adopted in a relatively short time. Therefore, the scope of literary techniques and attitudes deemed “modernist” was usually broad and included competing, sometimes oppositional, trends, but is often characterized by a sense of individualism and of crisis, and by a critique of the concepts of realism, progress, and linear time, as well as by a self-referential style. Aspects of both linguistic and formal playfulness opened modernism to influences from traditional literature and thus brought modernist literature into contact with other realms than in the West. Modernism flourished at different times and in comparable but different environments in various localities in the Sinophone world. Postmodernism was introduced to Taiwan, Hong Kong, and China around the mid-1980s, whereas postmodern literature and discourse emerged primarily in the 1990s. Postmodernism rejects the claims to legitimacy of modern logocentrism, stable identities, essentialism, and linear and developmental conceptions of time, as well as concluding ideologies and power structures. In literary practice, it is characterized by techniques such as metafiction, fabulation or hyperreality, fragmentation, bricoleur, pastiche, playfulness, nonlinear or spatial arrangements, intertextuality, parody, and dark humor. It highlights multiple interpretations, or even no coherence, in a single literary text. In China, modernism and postmodernism are simultaneous and overlapping phenomena. Various scholarly debates have evolved regarding chiefly the adoptability of both West-originated terms. They are critically negotiated as (semi-, neo-)colonial, as nationalist literature, as independent and own developments of both concepts, and as an indigenization. The question remains whether these Western terms can be meaningfully applied to describe Chinese, Taiwanese, or Hong Kongese cultural/literary phenomena. In any case, different sociohistorical settings resulted in an adaptation of these highly conscious and independent Western styles. (Post)modernism in the Sinophone world has boundaries different from those of its Western counterpart. It often comprises other forms and own manifestations.
Bone marrow metastasis of glioblastoma multiforme mimicking acute myeloid leukemia
Authors: Nagata Akihito , Kanemasa Yusuke , Kikuchi Miyu , Otani Ryohei , Yamada Ryoji , Motoi Toru , Tamura Taichi , Nakamura Shohei , Funasaka Chikako , Kageyama Akihiko , Shimoyama Tatsu , Shinoura Nobusada , Hishima Tsunekazu , Omuro Yasushi
Published: June 2020

A 46-year-old female patient with glioblastoma multiforme (GBM), IDH wild type developed severe pancytopenia 5 months after postoperative chemoradiotherapy. Bone marrow aspirate showed normocellular marrow with 70.0% abnormal cells, which suggested the possibility of acute myeloid leukemia. Immunophenotypic analysis did not show any hematological lineage markers, except for cluster of differentiation 56. The results of immunohistochemical staining of glial fibrillary acidic protein and oligodendrocyte transcription Factor 2 were positive. Based on these findings, the patient was diagnosed with bone marrow metastasis from GBM. Bone marrow metastasis from GBM is rare and little is known about the morphological characteristics of bone marrow aspiration smear findings. We experienced a rare case with marrow metastasis from GBM mimicking acute myeloid leukemia.
Pterygo-Maxillary Fissure as a Landmark for Localization of Internal Maxillary Artery for Use in Extracranial-Intracranial Bypass
Authors: Peto Ivo , Nouri Mohsen , Agazzi Siviero , Langer David , Dehdashti Amir R
Published: June 2020

BACKGROUND

Internal maxillary artery (IMax) is a relatively new donor vessel used in the extracranial-intracranial bypass surgery. However, unfamiliarity and relatively elaborate techniques of its harvest precluded its widespread use.

OBJECTIVE

To present a simplified technique of IMax harvest based on constant anatomical landmarks without the need of extensive skull-base drilling while providing adequate space for proximal anastomosis.

METHODS

Cadaveric dissection on 4 cadaveric heads (8 sides) was performed. Zygomatic osteotomy was performed and temporal muscle was dissected off the zygomatic process of the frontal bone and the frontal process of the zygomatic bone and reflected inferiorly into the bony gap created by the zygomatic osteotomy. Posterior wall of the maxilla (PWoM) was palpated. Following PWoM inferiorly leads to pterygo-maxillary fissure (PMF), which is a constant landmark IMax passes through.

RESULTS

IMax was localized following this technique before its entrance into PMF in every specimen. Proximal dissection was carried on to the exposed adequate length of the vessel. Depending on the relationship with the lateral pterygoid muscle, this might need to be incised to allow for identification of the IMax. After its transection, proximal stump is mobilized superiorly into the surgical field. Clinical application of this technique was demonstrated on an aneurysm case.

CONCLUSION

Using the palpation of the PWoM as a landmark for localization of PMF facilitates harvesting of IMax without need for extensive skull-base drilling and shortens the time of the surgery.
Does geodemographic segmentation explain differences in route of cancer diagnosis above and beyond person-level sociodemographic variables?
Authors: Bright C J , Gildea C , Lai J , Elliss-Brookes L , Lyratzopoulos G
Published: June 2020

Background

Emergency diagnosis of cancer is associated with poorer short-term survival and may reflect delayed help-seeking. Optimal targeting of interventions to raise awareness of cancer symptoms is therefore needed.

Methods

We examined the risk of emergency presentation of lung and colorectal cancer (diagnosed in 2016 in England). By cancer site, we used logistic regression (outcome emergency/non-emergency presentation) adjusting for patient-level variables (age, sex, deprivation and ethnicity) with/without adjustment for geodemographic segmentation (Mosaic) group.

Results

Analysis included 36 194 and 32 984 patients with lung and colorectal cancer. Greater levels of deprivation were strongly associated with greater odds of emergency presentation, even after adjustment for Mosaic group, which nonetheless attenuated associations (odds ratio [OR] most/least deprived group = 1.67 adjusted [model excluding Mosaic], 1.28 adjusted [model including Mosaic], P < 0.001 for both, for colorectal; respective OR values of 1.42 and 1.18 for lung, P < 0.001 for both). Similar findings were observed for increasing age. There was large variation in risk of emergency presentation between Mosaic groups (crude OR for highest/lowest risk group = 2.30, adjusted OR = 1.89, for colorectal; respective values of 1.59 and1.66 for lung).

Conclusion

Variation in risk of emergency presentation in cancer patients can be explained by geodemography, additional to deprivation group and age. The findings support proof of concept for public health interventions targeting all the examined attributes, including geodemography.
Latent Clinical-Anatomical Dimensions of Schizophrenia
Authors: Kirschner Matthias , Shafiei Golia , Markello Ross D , Makowski Carolina , Talpalaru Alexandra , Hodzic-Santor Benazir , Devenyi Gabriel A , Paquola Casey , Bernhardt Boris C , Lepage Martin , Chakravarty M Mallar , Dagher Alain , Mišić Bratislav
Published: June 2020

Widespread structural brain abnormalities have been consistently reported in schizophrenia, but their relation to the heterogeneous clinical manifestations remains unknown. In particular, it is unclear whether anatomical abnormalities in discrete regions give rise to discrete symptoms or whether distributed abnormalities give rise to the broad clinical profile associated with schizophrenia. Here, we apply a multivariate data-driven approach to investigate covariance patterns between multiple-symptom domains and distributed brain abnormalities in schizophrenia. Structural magnetic resonance imaging and clinical data were derived from one discovery sample (133 patients and 113 controls) and one independent validation sample (108 patients and 69 controls). Disease-related voxel-wise brain abnormalities were estimated using deformation-based morphometry. Partial least-squares analysis was used to comprehensively map clinical, neuropsychological, and demographic data onto distributed deformation in a single multivariate model. The analysis identified 3 latent clinical-anatomical dimensions that collectively accounted for 55% of the covariance between clinical data and brain deformation. The first latent clinical-anatomical dimension was replicated in an independent sample, encompassing cognitive impairments, negative symptom severity, and brain abnormalities within the default mode and visual networks. This cognitive-negative dimension was associated with low socioeconomic status and was represented across multiple races. Altogether, we identified a continuous cognitive-negative dimension of schizophrenia, centered on 2 intrinsic networks. By simultaneously taking into account both clinical manifestations and neuroanatomical abnormalities, the present results open new avenues for multi-omic stratification and biotyping of individuals with schizophrenia.
Long-term efficacy and tolerability of lemborexant compared with placebo in adults with insomnia disorder: results from the phase 3 randomized clinical trial SUNRISE 2
Authors: Kärppä Mikko , Yardley Jane , Pinner Kate , Filippov Gleb , Zammit Gary , Moline Margaret , Perdomo Carlos , Inoue Yuichi , Ishikawa Kohei , Kubota Naoki
Published: June 2020

Study Objectives

To assess long-term efficacy and safety of lemborexant (LEM), a novel dual orexin receptor antagonist, versus placebo in adults with insomnia disorder.

Methods

This was a 12-month, global, multicenter, randomized, double-blind, parallel-group phase 3 study comprising a 6-month placebo-controlled period (reported here) followed by a 6-month active-treatment-only period (reported separately). A total of 949 participants with insomnia (age ≥18 years) were randomized, received treatment with an oral dose of placebo or LEM (5 mg [LEM5] or 10 mg [LEM10]) and were analyzed. Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored throughout the study.

Results

Decreases from baseline in patient-reported (subjective) sleep onset latency and subjective wake after sleep onset, and increases from baseline in subjective sleep efficiency, were significantly greater with LEM5 and LEM10 versus placebo. Significant benefits over placebo were observed at the end of month 6, and at most time points assessed over the 6-month period, indicating long-term sustained efficacy of LEM. A significantly greater percentage of sleep onset responders and sleep maintenance responders were observed with LEM treatment versus placebo. Participants treated with LEM reported a significant improvement in quality of sleep after 6 months versus placebo. The majority of TEAEs were mild or moderate. There was a low rate of serious TEAEs and no deaths.

Conclusions

LEM5 and LEM10 provided significant benefit on sleep onset and sleep maintenance in individuals with insomnia disorder versus placebo, and was well tolerated.

Clinical trial registration

ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39
The Cumulative Indel Model: Fast and Accurate Statistical Evolutionary Alignment
Authors: De Maio Nicola
Published: June 2020

Sequence alignment is essential for phylogenetic and molecular evolution inference, as well as in many other areas of bioinformatics and evolutionary biology. Inaccurate alignments can lead to severe biases in most downstream statistical analyses. Statistical alignment based on probabilistic models of sequence evolution addresses these issues by replacing heuristic score functions with evolutionary model-based probabilities. However, score-based aligners and fixed-alignment phylogenetic approaches are still more prevalent than methods based on evolutionary indel models, mostly due to computational convenience. Here, I present new techniques for improving the accuracy and speed of statistical evolutionary alignment. The “cumulative indel model” approximates realistic evolutionary indel dynamics using differential equations. “Adaptive banding” reduces the computational demand of most alignment algorithms without requiring prior knowledge of divergence levels or pseudo-optimal alignments. Using simulations, I show that these methods lead to fast and accurate pairwise alignment inference. Also, I show that it is possible, with these methods, to align and infer evolutionary parameters from a single long synteny block ($\approx$530 kbp) between the human and chimp genomes. The cumulative indel model and adaptive banding can therefore improve the performance of alignment and phylogenetic methods. [Evolutionary alignment; pairHMM; sequence evolution; statistical alignment; statistical genetics.]
Defining Species When There is Gene Flow
Authors: Jiao Xiyun , Yang Ziheng
Published: June 2020

Whatever one’s definition of species, it is generally expected that individuals of the same species should be genetically more similar to each other than they are to individuals of another species. Here, we show that in the presence of cross-species gene flow, this expectation may be incorrect. We use the multispecies coalescent model with continuous-time migration or episodic introgression to study the impact of gene flow on genetic differences within and between species and highlight a surprising but plausible scenario in which different population sizes and asymmetrical migration rates cause a genetic sequence to be on average more closely related to a sequence from another species than to a sequence from the same species. Our results highlight the extraordinary impact that even a small amount of gene flow may have on the genetic history of the species. We suggest that contrasting long-term migration rate and short-term hybridization rate, both of which can be estimated using genetic data, may be a powerful approach to detecting the presence of reproductive barriers and to define species boundaries.[Gene flow; introgression; migration; multispecies coalescent; species concept; species delimitation.]
Equitable compensation and Brickenden: fiduciary loyalty and causation
Authors: Lee Jonathan T H
Published: June 2020

This article reconsiders the causation rules of equitable compensation for breaches of non-custodial fiduciary duties. It argues that these rules should correspond with and reflect the nature of fiduciary duties. Being a compensatory remedy, correct identification of the breach and the relevant counterfactual are therefore crucial. The failure to do so has led to much unwarranted criticism of the Privy Council’s decision in Brickenden. It also argues that a fiduciary is precluded by principle and policy from relying on the ‘escape route’ argument that the loss would have been suffered by his principal anyway.
Woody tissue photosynthesis increases radial stem growth of young poplar trees under ambient atmospheric CO2 but its contribution ceases under elevated CO2
Authors: De Roo Linus , Lauriks Fran , Salomón Roberto Luis , Oleksyn Jacek , Steppe Kathy
Published: June 2020

Woody tissue photosynthesis (Pwt) contributes to the tree carbon (C) budget and generally stimulates radial stem growth under ambient atmospheric CO2 concentration (aCO2). Moreover, Pwt has potential to enhance tree survival under changing climates by delaying negative effects of drought stress on tree hydraulic functioning. However, the relevance of Pwt on tree performance under elevated atmospheric CO2 concentration (eCO2) remains unexplored. To fill this knowledge gap, 1-year-old Populus tremula L. seedlings were grown in two treatment chambers at aCO2 and eCO2 (400 and 660 ppm, respectively), and woody tissues of half of the seedlings in each treatment chamber were light-excluded to prevent Pwt. Radial stem growth, sap flow, leaf photosynthesis and stomatal and canopy conductance were measured throughout the growing season, and the concentration of non-structural carbohydrates (NSC) in stem tissues was determined at the end of the experiment. Fuelled by eCO2, an increase in stem growth of 18 and 50% was observed in control and light-excluded trees, respectively. Woody tissue photosynthesis increased radial stem growth by 39% under aCO2, while, surprisingly, no impact of Pwt on stem growth was observed under eCO2. By the end of the growing season, eCO2 and Pwt had little effect on stem growth, leaf photosynthesis acclimated to eCO2, but stomatal conductance did not, and homeostatic stem NSC pools were observed among combined treatments. Our results highlight that eCO2 potentially fulfils plant C requirements, limiting the contribution of Pwt to stem growth as atmospheric [CO2] rises, and that radial stem growth in young developing trees was C (source) limited during early phenological stages but transitioned towards sink-driven control at the end of the growing season.
Predicting crash injury severity at unsignalized intersections using support vector machines and naïve Bayes classifiers
Authors: Arhin Stephen A , Gatiba Adam
Published: June 2020

The Washington, DC crash statistic report for the period from 2013 to 2015 shows that the city recorded about 41 789 crashes at unsignalized intersections, which resulted in 14 168 injuries and 51 fatalities. The economic cost of these fatalities has been estimated to be in the millions of dollars. It is therefore necessary to investigate the predictability of the occurrence of theses crashes, based on pertinent factors, in order to provide mitigating measures. This research focused on the development of models to predict the injury severity of crashes using support vector machines (SVMs) and Gaussian naïve Bayes classifiers (GNBCs). The models were developed based on 3307 crashes that occurred from 2008 to 2015. Eight SVM models and a GNBC model were developed. The most accurate model was the SVM with a radial basis kernel function. This model predicted the severity of an injury sustained in a crash with an accuracy of approximately 83.2%. The GNBC produced the worst-performing model with an accuracy of 48.5%. These models will enable transport officials to identify crash-prone unsignalized intersections to provide the necessary countermeasures beforehand.
The Host Range of Subgroup 16SrII-X Phytoplasma Extends to Globe Amaranth and Other Wild Plants in Saudi Arabia
Authors: Omar Ayman F. , Alsohim Abdullah S. , Al-jamhan Khaled A. , Pérez-López Edel
Published: June 2020

In recent years, the number of plant hosts affected by peanut witches’-broom group (16SrII) phytoplasma in Saudi Arabia has increased at a concerning speed. Since 2015 symptoms resembling phytoplasma-related diseases have been reported in Al-Qassim region affecting the wild plants globe amaranth, amaranthus, black nightshade, and buckthorn. Except for globe amaranth, which showed flower deformations, the other plants showed witches’ broom and little leaves. All the symptomatic samples collected in this study were positive for phytoplasma using universal primers targeting the 16S rRNA-encoding gene. Sequence analysis identified the phytoplasma as a member of the 16SrII-X subgroup, originally described in Saudi Arabia by our group. This is the first report of globe amaranth, amaranthus, black nightshade, and buckthorn as phytoplasma hosts in Saudi Arabia, and the first report worldwide of globe amaranth as a phytoplasma host and buckthorn being affected by 16SrII phytoplasma group.
Leveraging Tele-Critical Care Capabilities for Clinical Trial Consent
Authors: Ieronimakis Kristina M. , Cain Janell A. , Switzer Michael S. , Odineal David D. , Deacy Thomas K. , Stein Michael T. O. , Colombo Rhonda E. , Colombo Christopher J.
Published: June 2020

A severe coronavirus disease 2019 patient admitted to our institution for medical management was enrolled in a randomized placebo-controlled trial of an investigational therapeutic for coronavirus disease 2019. We leveraged existing video-telecommunication equipment to obtain informed consent. We found video-telecommunication use closely mirrored person-to-person contact for research consent by maintaining engagement and ensuring understanding. Video-telecommunication use facilitated clinical research while minimizing unnecessary exposure to coronavirus disease 2019 and conserving personal protective equipment. Prior to the coronavirus disease 2019 pandemic, research regulatory agencies were essentially silent on the matter of video-telecommunication consent. Regulatory guidance became available during the pandemic in response to increased isolation and social distancing practices. Virtual health and telemedicine use expanded greatly during the pandemic, and this increase will likely persist after the pandemic ends. We anticipate video-telecommunication adoption and implementation for research consent will also continue to grow after the coronavirus disease 2019 pandemic is over.
Conflict Management in the ICU
Authors: Kayser Joshua B. , Kaplan Lewis J.
Published: June 2020

Objectives:

To provide a concise review of data and literature pertaining to the etiologies of conflict in the ICU, as well as current approaches to conflict management.

Data Sources:

Detailed search strategy using PubMed and OVID Medline for English language articles describing conflict in the ICU as well as prevention and management strategies.

Study Selection:

Descriptive and interventional studies addressing conflict, bioethics, clinical ethics consultation, palliative care medicine, conflict management, and conflict mediation in critical care.

Data Extraction:

Relevant descriptions or studies were reviewed, and the following aspects of each manuscript were identified, abstracted, and analyzed: setting, study population, aims, methods, results, and relevant implications for critical care practice and training.

Data Synthesis:

Conflict frequently erupts in the ICU between patients and families and care teams, as well as within and between care teams. Conflict engenders a host of untoward consequences for patients, families, clinicians, and facilities rendering abrogating conflict a key priority for all. Conflict etiologies are diverse but understood in terms of a framework of triggers. Identifying and de-escalating conflict before it become intractable is a preferred approach. Approaches to conflict management include utilizing clinical ethics consultation, and palliative care medicine clinicians. Conflict Management is a new technique that all ICU clinicians may use to identify and manage conflict. Entrenched conflict appears to benefit from Bioethics Mediation, an approach that uses a neutral, unaligned mediator to guide parties to a mutually acceptable resolution.

Conclusions:

Conflict commonly occurs in the ICU around difficult and complex decision-making. Patients, families, clinicians, and institutions suffer undesirable consequences resulting from conflict, establishing conflict prevention and resolution as key priorities. A variety of approaches may successfully identify, manage, and prevent conflict including techniques that are utilizable by all team members in support of clinical excellence.
External Validation of an Acute Respiratory Distress Syndrome Prediction Model Using Radiology Reports
Authors: Mayampurath Anoop , Churpek Matthew M. , Su Xin , Shah Sameep , Munroe Elizabeth , Patel Bhakti , Dligach Dmitriy , Afshar Majid
Published: June 2020

Objectives:

Acute respiratory distress syndrome is frequently under recognized and associated with increased mortality. Previously, we developed a model that used machine learning and natural language processing of text from radiology reports to identify acute respiratory distress syndrome. The model showed improved performance in diagnosing acute respiratory distress syndrome when compared to a rule-based method. In this study, our objective was to externally validate the natural language processing model in patients from an independent hospital setting.

Design:

Secondary analysis of data across five prospective clinical studies.

Setting:

An urban, tertiary care, academic hospital.

Patients:

Adult patients admitted to the medical ICU and at-risk for acute respiratory distress syndrome.

Interventions:

None.

Measurements and Main Results:

The natural language processing model was previously derived and internally validated in burn, trauma, and medical patients at Loyola University Medical Center. Two machine learning models were examined with the following text features from qualifying radiology reports: 1) word representations (n-grams) and 2) standardized clinical named entity mentions mapped from the National Library of Medicine Unified Medical Language System. The models were externally validated in a cohort of 235 patients at the University of Chicago Medicine, among which 110 (47%) were diagnosed with acute respiratory distress syndrome by expert annotation. During external validation, the n-gram model demonstrated good discrimination between acute respiratory distress syndrome and nonacute respiratory distress syndrome patients (C-statistic, 0.78; 95% CI, 0.72–0.84). The n-gram model had a higher discrimination for acute respiratory distress syndrome when compared with the standardized named entity model, although not statistically significant (C-statistic 0.78 vs 0.72; p = 0.09). The most important features in the model had good face validity for acute respiratory distress syndrome characteristics but differences in frequencies did occur between hospital settings.

Conclusions:

Our computable phenotype for acute respiratory distress syndrome had good discrimination in external validation and may be used by other health systems for case-identification. Discrepancies in feature representation are likely due to differences in characteristics of the patient cohorts.
A new algorithm for the evaluation of recurrent pregnancy loss redefining unexplained miscarriage: review of current guidelines
Authors: Papas Ralph S. , Kutteh William H.
Published: June 2020

Purpose of review

Couples with recurrent pregnancy loss (RPL) are often referred to reproductive specialists to help determine the reason for their repeated losses. This review will help to develop a strategy that is effective in providing a diagnosis, efficient to administer, and cost-effective to the healthcare system.

Recent findings

International societies have published different recommendations for the evaluation of RPL, they consider it appropriate to initiate an evaluation after two (or three) clinical miscarriages. On the contrary, the clinician who follows these guidelines will only be able to offer a possible explanation to fewer than half of the couples being evaluated. Recently, genetic testing of miscarriage tissue using 24-chromosome microarray (CMA) analysis at the time of the second pregnancy loss coupled with testing based on society guidelines has been shown provide an explanation in more than 90% of cases.

New guidelines for the complete evaluation of RPL should consider adding 24-CMA testing on the miscarriage tissue. Providing couples with an explanation for recurrent loss assists them in dealing with the loss and discourages the clinician from instituting unproven therapies. Truly unexplained pregnancy loss can be reduced to less than 10% with this new algorithm. Incorporation of these strategies will result in significant cost savings to the healthcare system.
Pediatric Resident Engagement With an Online Critical Care Curriculum During the Intensive Care Rotation*
Authors: Daniel Dennis A. , Poynter Sue E. , Landrigan Christopher P. , Czeisler Charles A. , Burns Jeffrey P. , Wolbrink Traci A.
Published: June 2020

Objectives:

Residents are often assigned online learning materials as part of blended learning models, superimposed on other patient care and learning demands. Data that describe the time patterns of when residents interact with online learning materials during the ICU rotation are lacking. We describe resident engagement with assigned online curricula related to time of day and ICU clinical schedules, using website activity data.

Design:

Prospective cohort study examining curriculum completion data and cross-referencing timestamps for pre- and posttest attempts with resident schedules to determine the hours that they accessed the curriculum and whether or not they were scheduled for clinical duty. Residents at each site were cohorted based on two differing clinical schedules—extended duration (>24 hr) versus shorter (maximum 16 hr) shifts.

Setting:

Two large academic children’s hospitals.

Subjects:

Pediatric residents rotating in the PICU from July 2013 to June 2017.

Interventions:

None.

Measurements and Main Results:

One-hundred and fifty-seven pediatric residents participated in the study. The majority of residents (106/157; 68%) completed the curriculum, with no statistically significant association between overall curriculum completion and schedule cohort at either site. Residents made more test attempts at nighttime between 6 pm and 6 am (1,824/2,828; 64%) regardless of whether they were scheduled for clinical duty. Approximately two thirds of test attempts (1,785/2,828; 63%) occurred when residents were not scheduled to work, regardless of time of day. Forty-two percent of all test attempts (1,199/2,828) occurred between 6 pm and 6 am while off-duty, with 12% (342/2,828) occurring between midnight and 6 am.

Conclusions:

Residents rotating in the ICU completed online learning materials mainly during nighttime and off-duty hours, including usage between midnight and 6 am while off-duty. Increasing nighttime and off-duty workload may have implications for educational design and trainee wellness, particularly during busy, acute clinical rotations, and warrants further examination.