bluuebunny/crossref_metadata_2025 huggingface dataset:
Cobamide remodeling in the freshwater microalga Chlamydomonas reinhardtii
Authors: Baum Christoph , Menezes Riya C , Svatoš Aleš , Schubert Torsten
Published: October 2020

Microalgae are not able to produce cobamides (Cbas, B12 vitamers) de novo. Hence, the production of catalytically active Cba-containing methionine synthase (MetH), which is present in selected representatives, is dependent on the availability of exogenous B12 vitamers. Preferences in the utilization of exogenous Cbas equipped with either adenine or 5,6-dimethylbenzimidazole as lower base have been reported for some microalgae. Here, we investigated the utilization of norcobamides (NorCbas) for growth by the Cba-dependent Chlamydomonas reinhardtii mutant strain (ΔmetE). The growth yields in the presence of NorCbas were lower in comparison to those achieved with Cbas. NorCbas lack a methyl group in the linker moiety of the nucleotide loop. C. reinhardtii was also tested for the remodeling of NorCbas (e.g. adeninyl-norcobamide) in the presence of different benzimidazoles. Extraction of the NorCbas from C. reinhardtii, their purification, and identification confirmed the exchange of the lower base of the vitamers. However, the linker moiety of the NorCbas nucleotide loop was not exchanged. This observation strongly indicates the presence of an alternative mode of Cba deconstruction in C. reinhardtii that differs from the amidohydrolase (CbiZ)-dependent pathway described in Cba-remodeling bacteria and archaea.
International Law and Linguistics: Pieces of an Interdisciplinary Puzzle
Authors: Pirker Benedikt , Smolka Jennifer
Published: October 2020

In the framework of the empirical turn in international law, international lawyers are increasingly turning to specific linguistic theories to gain insights into language-related processes in international law, such as interpretation or law-making. The present article addresses these current, selective approaches by offering a broad overview and taxonomy of the most prominent and relevant directions of research in linguistics. It addresses in turn discourse analysis and text linguistics, syntax, semantics, pragmatics, historical linguistics and etymology, lexicography, corpus linguistics and computational linguistics, sociolinguistics and forensic linguistics, loosely following the phases of the ‘life cycle’ of international law in which they could most fruitfully be used to study and practise international law.
Quantifying the structure of strong gravitational lens potentials with uncertainty-aware deep neural networks
Authors: Vernardos Georgios , Tsagkatakis Grigorios , Pantazis Yannis
Published: October 2020

Gravitational lensing is a powerful tool for constraining substructure in the mass distribution of galaxies, be it from the presence of dark matter sub-haloes or due to physical mechanisms affecting the baryons throughout galaxy evolution. Such substructure is hard to model and is either ignored by traditional, smooth modelling, approaches, or treated as well-localized massive perturbers. In this work, we propose a deep learning approach to quantify the statistical properties of such perturbations directly from images, where only the extended lensed source features within a mask are considered, without the need of any lens modelling. Our training data consist of mock lensed images assuming perturbing Gaussian Random Fields permeating the smooth overall lens potential, and, for the first time, using images of real galaxies as the lensed source. We employ a novel deep neural network that can handle arbitrary uncertainty intervals associated with the training data set labels as input, provides probability distributions as output, and adopts a composite loss function. The method succeeds not only in accurately estimating the actual parameter values, but also reduces the predicted confidence intervals by 10 per cent in an unsupervised manner, i.e. without having access to the actual ground truth values. Our results are invariant to the inherent degeneracy between mass perturbations in the lens and complex brightness profiles for the source. Hence, we can quantitatively and robustly quantify the smoothness of the mass density of thousands of lenses, including confidence intervals, and provide a consistent ranking for follow-up science.
Mechanisms coordinating ribosomal protein gene transcription in response to stress
Authors: Zencir Sevil , Dilg Daniel , Rueda Maria Paula , Shore David , Albert Benjamin
Published: October 2020

While expression of ribosomal protein genes (RPGs) in the budding yeast has been extensively studied, a longstanding enigma persists regarding their co-regulation under fluctuating growth conditions. Most RPG promoters display one of two distinct arrangements of a core set of transcription factors (TFs) and are further differentiated by the presence or absence of the HMGB protein Hmo1. However, a third group of promoters appears not to be bound by any of these proteins, raising the question of how the whole suite of genes is co-regulated. We demonstrate here that all RPGs are regulated by two distinct, but complementary mechanisms driven by the TFs Ifh1 and Sfp1, both of which are required for maximal expression in optimal conditions and coordinated downregulation upon stress. At the majority of RPG promoters, Ifh1-dependent regulation predominates, whereas Sfp1 plays the major role at all other genes. We also uncovered an unexpected protein homeostasis-dependent binding property of Hmo1 at RPG promoters. Finally, we show that the Ifh1 paralog Crf1, previously described as a transcriptional repressor, can act as a constitutive RPG activator. Our study provides a more complete picture of RPG regulation and may serve as a paradigm for unravelling RPG regulation in multicellular eukaryotes.
Sustained Lung Inflation in Pre-term Infants at Birth: A Randomized Controlled Trial
Authors: Abuel Hamd Walaa A , El Sherbiny Douaa E , El Houchi Salma Z , Iskandar Iman F , Akmal Dina M
Published: October 2020

Background

Invasive mechanical ventilation (IMV) of pre-term infants may be associated with high rate of mortality and iatrogenic complications in low- and middle-income countries. Sustained lung inflation (SLI) may help to reduce their need for IMV.

Methods

This randomized controlled trial included 160 infants with gestational age (GA) ≥27 and ≤32 weeks who were randomly assigned to receive either SLI; using a pressure of 20 cmH2O for 15 s followed by nasal continuous positive airway pressure (CPAP) of 5 cmH2O or nasal CPAP alone, through an appropriate mask and a T-piece resuscitator. Primary outcome was the need for IMV in the first 72 h of life.

Results

There was no difference in the primary outcome between SLI group; 55% (44 out of 80) and the control group; 65% (52 out of 80) [odds ratio (OR): 0.623, 95% confidence interval (CI): 0.33–1.18; p = 0.145]. However, SLI significantly reduced the primary outcome in the sicker infants; who had clinical eligibility criteria (CEC; OR: 0.224, 95% CI: 0.076–0.663; p = 0.005) and in the smaller babies; whose GA was <30 weeks (OR: 0.183, 95% CI: 0.053–0.635; p = 0.005).

Conclusion

SLI was not harmful. Although, it did not lead to reduction in the need for IMV in the first 72 h of life in pre-term infants with GA ≥27 and ≤32 weeks, SLI reduced this outcome in the subgroup of infants with CEC and those with GA <30 weeks. Future trials are needed to investigate the effect of SLI on these two subgroups.

Trial registration

Clinical trials.gov, NCT03518762. https://www.clinicaltrials.gov/ct2/show/NCT03518762?term=NCT03518762&rank=1
Financial Inclusion and Stability: Review of Theoretical and Empirical Links
Authors: Čihák Martin , Mare Davide Salvatore , Melecky Martin
Published: October 2020

This paper reviews the literature on financial stability and financial inclusion—two broad objectives of financial policy that may be mutually dependent. The review suggests the possible co-dependence of stability and inclusion. We build on this theoretical motivation by exploring stylized facts (correlations) obtained from data sets that have been widely used in the literature on financial inclusion and stability. The empirical correlations suggest that, on average, financial inclusion and stability correlate negatively, but the correlations vary systematically across individuals, firms, and country contexts. Depending on the financial instrument and stability measure, positive correlations are also likely. These associations reflect some findings in the existing literature, but also point to knowledge gaps that can be addressed by future research.
Genome Sequence Resources for the Maize Pathogen Fusarium temperatum Isolated in Poland
Authors: Wit Marcin , Leng Yueqiang , Du Yang , Cegiełko Małgorzata , Jabłońska Emilia , Wakuliński Wojciech , Zhong Shaobin
Published: October 2020

Fusarium temperatum (Scaufl. & Munaut) is one of the most important fungal pathogens that cause ear and stalk rots in maize. In this study, we sequenced genomes of two F. temperatum isolates (KFI615 and KFI660) isolated from corn ears in Poland. A total of 110.3 and 116.3 million 100-nucleotide paired-end clean reads were obtained for KFI615 and KFI660, which were assembled into 20 and 18 scaffolds with an estimated genome size of 45.21 and 45.00 Mb, respectively. These genome sequences provide important resources for understanding pathogenicity and biology of the pathogens within the Fusarium fujikuroi complex.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Bowtie diagram: a simple tool for analysis and planning in anesthesia
Authors: Culwick Martin D. , Endlich Yasmin , Prineas Stavros N.
Published: October 2020

Purpose of review

The purpose is to show the advantages of a Bowtie diagram as a versatile tool for displaying and understanding the evolvement and management of critical incidents.

Recent findings

The Bowtie diagram has been used recently in anesthesia to depict critical incidents having been used in high-risk industries for several decades. This diagram displays the progression from latent factors to potential harm in five steps.

The Bowtie diagram combines the features of a fault tree and an event tree with the adverse event, known as the Top Event separating the two sections. The fault tree is similar in concept to a Swiss Cheese diagram and the event tree similar in concept to an emergency management algorithm. Preventive barriers and escalation measures are used to detect and trap abnormal states. If these fail, the event proceeds to a crisis, leading to the Top Event, a time for making decisions. A recovery state follows, which depicts an emergency state mandating immediate life or limb-saving management to recover from the crisis. Finally, in the aftermath state, a time for reflection and learning, ultimate outcomes are shown in the right-hand column.

Video abstract

The Bowtie Diagram. Designed and created by Yasmin Endlich, Martin D. Culwick and Stavros N. Prineas, http://links.lww.com/COAN/A68.
Modeling the Effect of Excitation on Depth of Anesthesia Monitoring in γ-Aminobutyric Acid Type A Receptor Agonist ABP-700
Authors: Valk Beatrijs I. , Eleveld Douglas J. , Meyer Peter , Meier Sascha , den Daas Izaak , van Amsterdam Kai , Campagna Jason A. , Sweeney Steven P. , Absalom Anthony R. , Struys Michel M. R. F.
Published: October 2020

Background

γ-Aminobutyric acid type A (GABAA) receptor agonists are known to cause involuntary muscle movements. The mechanism of these movements is not known, and its relationship to depth of anesthesia monitoring is unclear. We have explored the effect of involuntary muscle movement on the pharmacokinetic-pharmacodynamic model for the GABAA receptor agonist ABP-700 and its effects on the Bispectral Index (BIS) as well as the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scores.

Methods

Observations from 350 individuals (220 men, 130 women) were analyzed, comprising 6,312 ABP-700 concentrations, 5,658 ABP-700 metabolite (CPM-acid) concentrations, 25,745 filtered BIS values, and 6,249 MOAA/S scores, and a recirculatory model developed. Various subject covariates and pretreatment with an opioid or a benzodiazepine were explored as covariates. Relationships between BIS and MOAA/S models and involuntary muscle movements were examined.

Results

The final model shows that the pharmacokinetics of ABP-700 are characterized by small compartmental volumes and rapid clearance. The BIS model incorporates an effect-site for BIS suppression and a secondary excitatory/disinhibitory effect-site associated with a risk of involuntary muscle movements. The secondary effect-site has a threshold that decreases with age. The MOAA/S model did not show excitatory effects.

Conclusions

The GABAA receptor agonist ABP-700 shows the expected suppressive effects for BIS and MOAA/S, but also disinhibitory effects for BIS associated with involuntary muscle movements and reduced by pretreatment. Our model provides information about involuntary muscle movements that may be useful to improve depth of anesthesia monitoring for GABAA receptor agonists.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Pediatric Radial Neck Fractures: Which Ones Can Be Successfully Closed Reduced in the Emergency Department?
Authors: Kong Justin , Lewallen Laura , Elliott Marilyn , Jo ChanHee , McIntosh Amy L. , Ho Christine A.
Published: October 2020

Background:

The purpose of this study is to examine pediatric patients with a radial neck fracture and determine the factors associated with a failed closed reduction (CR) in the emergency department (ED).

Methods:

A total of 70 patients with acute radial neck fractures were retrospectively reviewed. Inclusion criteria were: age 18 years or younger at time of injury, diagnosis of radial neck fracture without other associated elbow fractures, an attempt at CR with manipulation in the ED or immediate surgery, open proximal radial physis, and appropriate imaging to categorize the injury. Charts were reviewed and demographic data was obtained. Initial injury films were reviewed and the Judet classification was used to define fracture types/categories.

Results:

CR was attempted on 41 patients. Twenty-nine patients went straight to surgery without a CR attempt. Compared with patients that had an attempted CR in the ED, patients that went straight to surgery had longer mean time from injury to ED presentation (5.6 d; P=0.0001), greater mean fracture angulation (55.0 degrees; P=0.001), and greater fracture translation (46.2%; P=0.001). When analyzing the patients that had a CR attempted in the ED, univariate statistical analysis demonstrated that ≥Judet 4 classification (P=0.03), greater amounts of fracture angulation (P=0.003), and a treatment delayed >24 hours from injury (P=0.007) were significant risk factors for failure of CR in the ED. Zero (0/10) patients with fracture angulation ≥60 degrees had a successful CR. Only 1/14 patients presenting >24 hours after injury had a successful CR in the ED.

Conclusions:

Circumventing sedation in the ED, and instead splinting for a planned surgical intervention may be a more efficient treatment method for pediatric radial neck fractures that present to the ED>24 hours after injury and/or have angulations ≥60 degrees. Adopting this new strategy may save time, reduce costs, and avoid possible harm/complications associated with sedation in the ED.

Level of Evidence:

Level III—prognostic.
Predictor of Surgical Outcomes in Ankylosing Spondylitis Cervical Spinal Fracture
Authors: Gao Qichang , Zhang Zhizhuang , Shao Tuo , Tang Weilong , Hu Yuhang , Sheng Hongtao , Gu Jiaao , Yu Zhange
Published: October 2020

Study Design.

Retrospective study.

Objective.

A retrospective study was conducted to clarify the prognostic factors of postoperative for cervical spine fractures patients with ankylosing spondylitis (AS).

Summary of Background Data.

Now the high probability of cervical fractures in patients with AS is unanimously recognized. Fractures mostly occur in the lower cervical spine and two-thirds of patients are accompanied by spinal cord injury. But there are few studies on treatment of AS patients with cervical fracture and it is unclear whether the surgical method, timing of surgery, basic treatment of AS, and different doses of steroids therapy have an impact on the prognosis. Thus, this study aims to evaluate the impact of perioperative factors on the prognosis of traumatic cervical fractures in surgical patients with AS.

Methods.

Preoperative and postoperative spinal cord function were assessed according to the Japanese Orthopaedic Association (JOA) Scores and Improvement rate were calculated. The neck pain severity were rated using a visual analogue scale (VAS) score. The t test and v2-test were used for comparison of clinical data between the preoperative and postoperative groups. Logistic univariate and multivariate regression analysis were used to obtain adjusted odds ratios. Pearson correlation coefficients were used to evaluate the relationship between variables.

Results.

The degree of fracture displacement in cervical spine fractures patients with AS was most common at the neck–chest junction (26.1%). Patients with degree of cervical fracture displacement less than 50% had significantly improved JOA scores after surgery (P = 0). The incidence of spinal cord injury (SCI) due to fracture was high (52.2%). Patients with combined anterior and posterior is helpful for neurological recovery (P = 0.01). Basic AS treating before injury would be benefit for neurological improvement (P = 0).

Conclusion.

Basic AS treatment, SCI, and surgical methods are independent factors that affect the prognosis of cervical spine fractures patients with AS. It is controversial to perform surgery and preoperative steroid application as soon as possible.

Level of Evidence: 3
Allograft-Composite Reverse Shoulder Arthroplasty for Malignant Tumor of the Proximal Humerus
Authors: Degeorge Benjamin , Chammas Michel , Coulet Bertrand , Daumillare Alexandre , Lazerges Cyril
Published: October 2020

Composite-allograft reverse shoulder arthroplasties are a surgical alternative in malignant tumor reconstructions following segmental bone resection of the proximal humerus. They allow reinsertion of the rotator cuff tendons and reliable restoration of humeral height, increasing prosthetic stability and mobility. Preoperative local tumor extension assessment must be thorough and a strict surgical technique must be followed to obtain satisfactory functional results. The indications for this procedure include a strictly intraosseous tumor of the proximal humerus corresponding to an S3-S4 A resection following criteria provided by the Musculoskeletal Tumor Society as described by Enneking and colleagues in 1990. Certain conditions must question the procedure such as extended S3-S4-S5 bone resections, partial sacrifice of the deltoid muscle, preoperative deltoid impairment, and glenohumeral arthrectomy. Here, we report technical details and indications of composite-allograft reverse shoulder arthroplasty in the context of tumor segmental resection of the proximal humerus, especially in the humeral preparation.
Characterizing the Patients, Hospitals, and Data Quality of the eICU Collaborative Research Database*
Authors: O’Halloran Heather M. , Kwong Kenneth , Veldhoen Richard A. , Maslove David M.
Published: October 2020

Objectives:

The eICU Collaborative Research Database is a publicly available repository of granular data from more than 200,000 ICU admissions. The quantity and variety of its entries hold promise for observational critical care research. We sought to understand better the data available within this resource to guide its future use.

Design:

We conducted a descriptive analysis of the eICU Collaborative Research Database, including patient, practitioner, and hospital characteristics. We investigated the completeness of demographic and hospital data, as well as those values required to calculate an Acute Physiology and Chronic Health Evaluation score. We also assessed the rates of ventilation, intubation, and dialysis, and looked for potential errors in the vital sign data.

Setting:

American ICUs that participated in the Philips Healthcare eICU program between 2014 and 2015.

Patients:

A total of 139,367 individuals who were admitted to one of the 335 participating ICUs between 2014 and 2015.

Interventions:

None.

Measurements and Main Results:

Most encounters were from small- and medium-sized hospitals, and managed by nonintensivists. The median ICU length of stay was 1.57 days (interquartile range, 0.82–2.97 d). The median Acute Physiology and Chronic Health Evaluation IV-predicted ICU mortality was 2.2%, with an observed mortality of 5.4%. Rates of ventilation (20–33%), intubation (15–24%), and dialysis (3–5%) varied according to the query method used. Most vital sign readings fell into realistic ranges, with manually curated data less likely to contain implausible results than automatically entered data.

Conclusions:

Data in the eICU Collaborative Research Database are for the most part complete and plausible. Some ambiguity exists in determining which encounters are associated with various interventions, most notably mechanical ventilation. Caution is warranted in extrapolating findings from the eICU Collaborative Research Database to larger ICUs with higher acuity.
Effect of Driving Pressure Change During Extracorporeal Membrane Oxygenation in Adults With Acute Respiratory Distress Syndrome: A Randomized Crossover Physiologic Study*
Authors: Del Sorbo Lorenzo , Goffi Alberto , Tomlinson George , Pettenuzzo Tommaso , Facchin Francesca , Vendramin Alice , Goligher Ewan C. , Cypel Marcelo , Slutsky Arthur S. , Keshavjee Shaf , Ferguson Niall D. , Fan Eddy ,   for the International ECMO Network (ECMONet)
Published: October 2020

Objectives:

Venovenous extracorporeal membrane oxygenation is an effective intervention to improve gas exchange in patients with severe acute respiratory distress syndrome. However, the mortality of patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation remains high, and this may be due in part to a lack of standardized mechanical ventilation strategies aimed at further minimizing ventilator-induced lung injury. We tested whether a continuous positive airway pressure ventilation strategy mitigates ventilator-induced lung injury in patients with severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation, compared with current ventilation practice that employs tidal ventilation with limited driving pressure. We used plasma biomarkers as a surrogate outcome for ventilator-induced lung injury.

Design:

Randomized crossover physiologic study.

Setting:

Single-center ICU.

Patients:

Ten patients with severe acute respiratory distress syndrome supported on venovenous extracorporeal membrane oxygenation.

Interventions:

The study included four phases. After receiving pressure-controlled ventilation with driving pressure of 10 cm H2O for 1 hour (phase 1), patients were randomly assigned to receive first either pressure-controlled ventilation 20 cm H2O for 2 hours (phase 2) or continuous positive airway pressure for 2 hours (phase 3), and then crossover to the other phase for 2 hours; during phase 4 ventilation settings returned to baseline (pressure-controlled ventilation 10 cm H2O) for 4 hours.

Measurements and Main Results:

There was a linear relationship between the change in driving pressure and the plasma concentration of interleukin-6, soluble receptor for advanced glycation end products, interleukin-1ra, tumor necrosis factor alpha, surfactant protein D, and interleukin-10.

Conclusions:

Ventilator-induced lung injury may occur in acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation despite the delivery of volume- and pressure-limited mechanical ventilation. Reducing driving pressure to zero may provide more protective mechanical ventilation in acute respiratory distress syndrome patients supported with venovenous extracorporeal membrane oxygenation. However, the risks versus benefits of such an approach need to be confirmed in studies that are designed to test patient centered outcomes.
Frequency and Implications of Complications in the ICU After Status Epilepticus: No Calm After the Storm*
Authors: Baumann Sira M. , Semmlack Saskia , De Marchis Gian Marco , Hunziker Sabina , Rüegg Stephan , Marsch Stephan , Sutter Raoul
Published: October 2020

Objectives:

To investigate the frequency, types, and implications of complications during intensive care in patients after status epilepticus has been successfully terminated.

Design:

Retrospective study.

Setting:

ICUs at a Swiss tertiary academic medical care center.

Patients:

Data were collected from the digital patient records of all adult patients with status epilepticus from 2012 to 2018.

Interventions:

None.

Methods:

Primary outcomes were defined as frequency of complications following status epilepticus termination and return to premorbid functional baseline. Univariable analyses regarding the relative risks of complications occurring after status epilepticus termination for no return to premorbid neurologic function were estimated by Poisson regression with robust error variance.

Results:

Of 311 patients with status epilepticus, 224 patients (72%) were treated on the ICU for more than 24 hours following status epilepticus termination. Ninety-six percent of patients remained in a prolonged state of altered consciousness for a median of 2 days (interquartile range, 1–3 d) and 80% had complications during their ICU treatment. Fifty-five percent had new-onset delirium with a median duration of 2 days (interquartile range, 1–3 d). Forty-two percent had mechanical ventilation for a median of 4 days (interquartile range, 2–11 d) and 21% had nosocomial infections diagnosed after status epilepticus. Multivariable analyses revealed that mechanical ventilation for more than 24 hours after status epilepticus, and arterial hypotension requiring vasopressors were independently associated with increased risk of no return to premorbid function (RRfor each additional day = 1.01; 95% CI, 1.02–1.03 and RRfor each additional day = 1.03; 95% CI, 1.01–1.05) and death (RRfor each additional day = 1.11; 95% CI, 1.04–1.19 and RRfor each additional day = 1.15; 95% CI, 1.03–1.28). Delirium was independently associated with a decreased relative risk of death (RRfor each additional day = 0.55; 95% CI, 0.37–0.80), but prolonged ICU- and hospital stays.

Conclusions:

Complications after status epilepticus termination are frequent and associated with no return to premorbid function, death, and prolonged ICU- and hospital stays. These results call for heightened awareness and further studies mainly regarding prediction and preventive strategies in this context.
Early Sepsis Prediction Using Ensemble Learning With Deep Features and Artificial Features Extracted From Clinical Electronic Health Records
Authors: He Zhengling , Du Lidong , Zhang Pengfei , Zhao Rongjian , Chen Xianxiang , Fang Zhen
Published: October 2020

Objectives:

Sepsis is caused by infection and subsequent overreaction of immune system and will severely threaten human life. The early prediction is important for the treatment of sepsis. This report aims to develop an early prediction method for sepsis 6 hours ahead on the basis of clinical electronic health records.

Data Sources:

Challenge data are released by PhysioNet/Computing in Cardiology Challenge 2019 and obtained from ICU patients in three separate hospital systems. Part of the data from two datasets, including 40,336 subjects, are publicly available, and the remaining are used as hidden test set. A normalized utility score defined by the organizing committee is used for model performance evaluation.

Study Selection:

The supervised machine learning is applied to tackle this challenge. Specifically, we establish the prediction model under the framework of ensemble learning by integrating the artificial features based on clinical prior knowledge of sepsis with deep features automatically extracted by long short-term memory neural network.

Data Extraction:

Forty clinical variables, including eight vital signs, 26 laboratory values, and six demographics, were measured and recorded once an hour for each individual, and the binary label (0 or 1) was simultaneously provided for each item.

Data Synthesis:

The proposed model was evaluated by 30-fold cross-validation. The sensitivity, specificity, and normalized utility score were 0.641 ± 0.022, 0.844 ± 0.007, and 0.401 ± 0.019 on publicly available datasets, respectively. The final normalized utility score our team (UCAS_DataMiner) has obtained was 0.313 on full hidden test set (0.406, 0.373, and –0.215 on test set A, B, and C, respectively).

Conclusions:

We realized a 6-hour ahead early-onset prediction of sepsis on the basis of clinical electronic health record by ensemble learning. The results indicated the proposed model functioned well in the early prediction of sepsis. In particular, ensemble learning had a significant (p < 0.01) improvement than any single model in performance.
Concurrent β-blocker Use is Associated With Improved Outcome in Esophageal Cancer Patients Who Undergo Chemoradiation
Authors: Farrugia Mark K. , Ma Sung Jun , Mattson David M. , Flaherty Leayn , Repasky Elizabeth A. , Singh Anurag K.
Published: October 2020

Background:

β-blocker use has been associated with improved outcomes in a number of different malignancies; however, the impact of β-blockade in esophageal cancer is not been well characterized. We compared the outcomes of esophageal cancer patients based on β-blocker usage.

Methods:

The charts of all 418 patients treated with radiation for esophageal cancer at our institution from April 2010 to October 2018 were analyzed. Patients who underwent treatment with palliative intent or did not finish treatment were excluded. β-blocker use was determined from the medication list at time of pretreatment consultation.

Results:

There were 291 esophageal cancer patients who received neoadjuvant/definitive chemoradiation therapy. The median follow-up for the cohort was 22.5 months (interquartile range: 9.6 to 41.0 mo). Within the cohort, 27.8% (n=81) of patients were taking β-blockers at the time of treatment. Those taking β-blockers had significantly improved distant control (22.2% vs. 37.9%; P=0.035). Concomitant β-blocker use was significantly associated with improved progression-free survival (P<0.001, hazard ratio=0.42 [0.27-0.66]) and overall survival (P=0.002, hazard ratio=0.55 [0.38-0.81]) on Cox regression analysis. Propensity score–matched pairs were created using tumor stage, nodal stage, sex, neoadjuvant versus definitive therapy, Karnofsky Performance Status, and aspirin use. This matched-pair analysis showed a significant progression-free survival (P=0.005) benefit in esophageal cancer patients taking β-blockers.

Conclusions:

Concurrent β-blocker use is common within patients receiving concurrent chemoradiation for esophageal cancer. Esophageal cancer patients who received chemoradiation while taking β-blockers demonstrated significant benefits in survival-based outcomes.
Effectiveness of Containment Measures Against COVID-19 in Singapore
Authors: Pung Rachael , Cook Alex R. , Chiew Calvin J. , Clapham Hannah E. , Sun Yinxiaohe , Li Zongbin , Dickens Borame L. , Ma Stefan , Mak Kenneth , Tan Chorh Chuan , Heng Derrick , Chen Mark I-Cheng , Lee Vernon J.
Published: October 2020

Background:

We hypothesize that comprehensive surveillance of COVID-19 in Singapore has facilitated early case detection and prompt contact tracing and, with community-based measures, contained spread. We assessed the effectiveness of containment measures by estimating transmissibility (effective reproduction number,

JOURNAL/epide/04.03/00001648-202101000-00011/inline-graphic1/v/2023-09-08T094005Z/r/image-tiff

) over the course of the outbreak.

Methods:

We used a Bayesian data augmentation framework to allocate infectors to infectees with no known infectors and determine serial interval distribution parameters via Markov chain Monte Carlo sampling. We fitted a smoothing spline to the number of secondary cases generated by each infector by respective onset dates to estimate

JOURNAL/epide/04.03/00001648-202101000-00011/inline-graphic2/v/2023-09-08T094005Z/r/image-tiff

and evaluated increase in mean number of secondary cases per individual for each day’s delay in starting isolation or quarantine.

Results:

As of April 1, 2020, 1000 COVID-19 cases were reported in Singapore. We estimated a mean serial interval of 4.6 days [95% credible interval (CI) = 4.2, 5.1] with a SD of 3.5 days (95% CI = 3.1, 4.0). The posterior mean

JOURNAL/epide/04.03/00001648-202101000-00011/inline-graphic3/v/2023-09-08T094005Z/r/image-tiff

was below one for most of the time, peaking at 1.1 (95% CI = 1.0, 1.3) on week 9 of 2020 due to a spreading event in one of the clusters. Eight hundred twenty-seven (82.7%) of cases infected less than one person on average. Over an interval of 7 days, the incremental mean number of cases generated per individual for each day’s delay in starting isolation or quarantine was 0.03 cases (95% CI = 0.02, 0.05).

Conclusions:

We estimate that robust surveillance, active case detection, prompt contact tracing, and quarantine of close contacts kept

JOURNAL/epide/04.03/00001648-202101000-00011/inline-graphic4/v/2023-09-08T094005Z/r/image-tiff

below one.
Simultaneous Quantification of BCR-ABL and Bruton Tyrosine Kinase Inhibitors in Dried Plasma Spots and Its Application to Clinical Sample Analysis
Authors: Mukai Yuji , Yoshida Yuka , Yoshida Tatsunari , Kondo Takeshi , Inotsume Nobuo , Toda Takaki
Published: October 2020

Background:

Recent reports highlight the importance of therapeutic drug monitoring (TDM) of BCR-ABL and Bruton tyrosine kinase inhibitors (TKIs); thus, large-scale studies are needed to determine the target concentrations of these drugs. TDM using dried plasma spots (DPS) instead of conventional plasma samples is a promising approach. This study aimed to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of BCR-ABL and Bruton TKIs for further TDM studies.

Methods:

A 20-μL aliquot of plasma was spotted onto a filter paper and dried completely. Analytes were extracted from 2 DPS using 250 μL of solvent. After cleanup by supported liquid extraction, the sample was analyzed by LC-MS/MS. Applicability of the method was examined using samples of patients' DPS transported by regular mail as a proof-of-concept study. The constant bias and proportional error between plasma and DPS concentrations were assessed by Passing–Bablok regression analysis, and systematic errors were evaluated by Bland–Altman analysis.

Results:

The method was successfully validated over the following calibration ranges: 1–200 ng/mL for dasatinib and ponatinib, 2–400 ng/mL for ibrutinib, 5–1000 ng/mL for bosutinib, and 20–4000 ng/mL for imatinib and nilotinib. TKI concentrations were successfully determined for 93 of 96 DPS from clinical samples. No constant bias between plasma and DPS concentrations was observed for bosutinib, dasatinib, nilotinib, and ponatinib, whereas there were proportional errors between the plasma and DPS concentrations of nilotinib and ponatinib. Bland–Altman plots revealed that significant systematic errors existed between both methods for bosutinib, nilotinib, and ponatinib.

Conclusions:

An LC-MS/MS method for the simultaneous quantification of 6 TKIs in DPS was developed and validated. Further large-scale studies should be conducted to assess the consistency of concentration measurements obtained from plasma and DPS.
Cardiomyopathies in Pregnancy: Etiologies and Management Strategies
Authors: BRILLER JOAN , VAUGHT ARTHUR J.
Published: October 2020

The cardiomyopathies are a diverse group of disorders characterized by structural abnormalities of heart muscle, many of which have a genetic component. They are associated with substantial morbidity and mortality in pregnancy. We review the distinct forms of cardiomyopathy (dilated, hypertrophic, and functional) which can be seen during pregnancy, discuss complications associated with each distinct group such as heart failure, arrhythmias, and transmission to offspring, and address management strategies for stable and unstable patients.
What Every Gynecologist Should Know About Perimenopause
Authors: VERRILLI LAUREN , BERGA SARAH L.
Published: October 2020

Perimenopause often represents a physiologically challenging phase in women’s lives. The clinical presentation of the perimenopause includes infertility, irregular menstrual cycles, menorrhagia, and new onset of or worsening of mood disorders. Unlike menopause, which is characterized by low levels of estradiol and progesterone, the hallmark of perimenopause is highly variable levels of estradiol and progesterone with abrupt increases and decreases that are often described as a hormonal roller coaster. This chapter invites general gynecologists to understand the hormonal basis of the common complaints of perimenopause and offers information about the physiology of these issues and helpful treatment options.
Temporal Attenuation of Gamma Dose Rate in Air Due to Radiocesium Downward Mobility in Soil
Authors: Velasco Hugo
Published: October 2020

The Chernobyl and Fukushima Dai-ichi Nuclear Power Plant accidents have demonstrated that radiocesium deposited on the ground was one of most important pathway contributions to the air dose rate. Cesium-134 contributes more significantly in the first period of 2–3 y. However, 137Cs external exposure may remain relevant for decades. The contribution to the air dose rate attributable to these radionuclides is maximum at the deposition time and then usually decreases over time. The dose rate temporal reduction is a consequence of both the radionuclide physical decay and the radionuclide downward mobility in soil. In this investigation, this decreasing behavior of the air dose rate is approached using an empirical attenuation function, and its coefficients are computed in terms of the effective diffusion coefficient and downward migration rates of radiocesium in soil. The methodology is tested for different hypothetical scenarios and in real situations, including areas affected by the two major accidents at nuclear power plants.
Least Significant Changes and Reproducibility of 131I Uptake Test
Authors: Şahmaran Turan , Gültekin Salih Sinan
Published: October 2020

Radioactive iodine uptake (RAIU) is one of the important tests performed in the departments of nuclear medicine, testing thyroid function by measuring the amount of 131I uptake after oral administration. A RAIU value measured 4 and 24 h after administration has been widely used for differential diagnosis of thyroid function and for the calculation of treatment dose. This study was performed to define practical methods for reproducibility and least significant change (LSC) values replicating thyroid measurements. In the study were 119 patients referred to the nuclear medicine department for examination of thyroid gland function with the diagnosis of Graves' disease (60), toxic multinodular goiter (29), thyroiditis (10), thyroid cancer (6), and unknown etiology (14). The level of thyroid stimulating hormone (TSH) among the patients was 2.07 ± 6.74 μIU mL−1. RAIU measurements were carried out by two different technicians, who have performed an equal number of measurements from each diagnosis in reference to the clinical diagnosis. Measurement of each patient was performed twice at 4 and 24 h after the administration under stable geometry and counting conditions using a standard procedure. Data were evaluated using statistical methods. For assessment of the reproducibility, three parameters were used: reproducibility coefficient (RC), the root-mean-square standard deviation (SDRMS), and the least significant change values. The average RAIU values of the first and second measurements were found as 23.71 ± 16.52% and 23.94 ± 16.64% at 4 h (p >0.05), and 35.33 ± 19.22% and 35.49 ± 19.19% at 24 h (p >0.05), respectively. For thyroid uptake values repeated at 4 and 24 h after radioiodine administration, the mean difference was found to be −0.24 ± 0.62% [limits of agreement (%); −1.44 to 0.97] at 4 h and −0.16 ± 0.44% [limits of agreement (%); −1.02 to 0.70] at 24 h. Confidence intervals were within the limits of agreement (d̅−1.96 SD and d̅+1.96 SD). When the correlation between the repeated RAIU measurements was examined taking the differences and averages into account, there was a negative correlation between 4-h measurement pairs (r=−0.203, p <0.05). On the other hand, a significant correlation was not found between the 24-h measurement pairs (r=0.074, p >0.05). RC, SDRMS, and LSC were calculated as 0.70%, 0.46%, and 1.29% for the 4 h measurements and 0.54%, 0.33%, and 0.91% for the 24-h measurements, respectively. Although there was a minor difference between measurement pairs at 4 and 24 h post-administration, the difference appeared to be insignificant without an apparent effect in the clinical settings.
Exposure to Short Wavelength-Enriched White Light and Exercise Improves Alertness and Performance in Operational NASA Flight Controllers Working Overnight Shifts
Authors: Barger Laura K. , Sullivan Jason P. , Lockley Steven W. , Czeisler Charles A.
Published: October 2020

Objective:

We evaluated the efficacy of a combined short-wavelength-enriched white light and exercise fatigue countermeasure during breaks for flight controllers working overnight shifts.

Methods:

Twenty NASA flight controllers were studied for two blocks of nightshifts in ISS mission control, randomized to either the control or countermeasure condition. The countermeasure constituted passive exposure to blue-enriched polychromatic lighting for three 20-minute intervals, which included 10 minutes of exercise and occurred before and twice during their shifts. Alertness, performance, and mood were evaluated.

Results:

Flight controllers reported being significantly more alert (P < 0.0001) and happy (P = 0.003) and had faster reaction times (10% slowest responses; P < 0.05) during the countermeasure condition compared to control.

Conclusions:

The combined light and exercise countermeasure improved alertness, performance, and mood in shift workers overnight. Further research is necessary to determine their relative contribution.
Doctor of Physical Therapy Students' Developing Understanding of Physical Therapy Practice: A Longitudinal Study
Authors: Gilliland Sarah J. , Brown Teressa F.
Published: October 2020

Introduction.

Clinical reasoning is a complex real-world practice that requires problem framing prior to problem solving. Clinicians and students demonstrate qualitative differences in their approaches to clinical reasoning that are influenced by their beliefs about practice. The purpose of this study was to examine the development of Doctor of Physical Therapy (DPT) students' perspectives on physical therapy practice throughout their entry-level education.

Methods.

A total of 44 students completed semistructured interviews that included both general and specific descriptions of their perceptions of physical therapy practice at 3 points during their DPT education: first, third, and eighth semester. The qualitative process of thematic analysis was used to identify patterns in the interview data. Patterns of change at both the group and individual levels within each coding dimension were identified.

Results.

First-semester students demonstrated a biomedical perspective focused on fixing problems related to specific pathologies while prioritizing the physical therapist's medical knowledge. Eighth semester students demonstrated a broader spectrum of perspectives with some retaining a biomedical view and others recognizing a more collaborative approach to practice with an emphasis on patient education and empowerment. There were high levels of variation in student development that became more pronounced as students moved through the curriculum.

Discussion and Conclusions.

Students' perspectives become more divergent over the 3 years in the program suggesting that natural development through classroom and clinical learning may not be sufficient for some students to develop comprehensive, patient-centered perspectives. The inconsistencies in development suggest that programs may need to give more explicit attention to students' development of perspectives/understandings in order to foster comprehensive development of patient-centered clinicians.
Bilateral Sequential Spontaneous Otogenic Pneumocephalus, Lessons in Pathophysiology, and Management of a Rare Case
Authors: Shapiro Scott B. , Lipschitz Noga , Tumlin Parker , Krueger Bryan , Forbes Jonathan , Samy Ravi N.
Published: October 2020

Objective:

Report the details of an unusual case of initially unilateral intradural spontaneous otogenic pneumocephalus in which the patient developed contralateral pneumocephalus after surgical repair of temporal bone and dural defects on the initial side. Discuss the lessons learned concerning management and pathophysiology of this rare case.

Patient:

A 73-year-old male presenting with bilateral retro-orbital pain and headache was found to have unilateral intradural pneumocephalus in the temporal lobe with an adjacent defect in the temporal bone.

Intervention:

Surgical repair of the initial defect in the temporal bone and dura via a middle cranial fossa approach with obliteration of the mastoid cavity.

Results:

The patient's symptoms and degree of pneumocephalus on first affected side decreased initially after surgery. Two weeks after surgery he developed worsening pneumocephalus on the contralateral side in the temporal and frontal lobes with weakness and mild somnolence. This side was repaired via a similar technique without mastoid obliteration. Two weeks after surgery the patient recovered to normal level of consciousness with mild residual weakness.

Conclusions:

Spontaneous otogenic intradural pneumocephalus is an extremely rare but serious condition related to defects in the temporal bone and dura. The precise mechanism by which this occurs is poorly understood. This unusual case where there were bilateral defects presenting with spontaneous otogenic pneumocephalus in sequence illustrates that it represents a rare sequelae of processes which thin the skull base. These processes should be addressed in addition to acute management of the defect and intracranial air.
Middle Ear Actuator Performance Determined From Intracochlear Pressure Measurements in a Single Cochlear Scala
Authors: Raufer Stefan , Gamm Ute A. , Grossöhmichen Martin , Lenarz Thomas , Maier Hannes
Published: October 2020

Hypothesis:

Intracochlear pressure measurements in one cochlear scala are sufficient as reference to determine the output of an active middle ear implant (AMEI) in terms of “equivalent sound pressure level” (eqSPL).

Background:

The performance of AMEIs is commonly calculated from stapes velocities or intracochlear pressure differences (PDiff). However, there are scenarios where measuring stapes velocities or PDiff may not be feasible, for example when access to the stapes or one of the scalae is impractical.

Methods:

We reanalyzed data from a previous study of our group that investigated the performance of an AMEI coupled to the incus in 10 human temporal bones. We calculated eqSPL based on stapes velocities according to the ASTM standard F2504-05 and based on intracochlear pressures in scala vestibuli, scala tympani, and PDiff.

Results:

The AMEI produced eqSPL of ∼100 to 120 dB at 1 Vrms. No significant differences were found between using intracochlear pressures in scala vestibuli, scala tympani, or PDiff as a reference. The actuator performance calculated from stapes displacements predicted slightly higher eqSPLs at frequencies above 1000 Hz, but these differences were not statistically significant.

Conclusion:

Our findings show that pressure measurements in one scala can be sufficient to evaluate the performance of an AMEI coupled to the incus. The method may be extended to other stimulation modalities of the middle ear or cochlea when access to the stapes or one of the scalae is not possible.