bluuebunny/crossref_metadata_2025 huggingface dataset:
Density weighted angular redshift fluctuations: a new cosmological observable
Authors: Hernández–Monteagudo Carlos , Chaves-Montero Jonás , Angulo Raúl E
Published: October 2020

We propose the use of angular fluctuations in the galaxy redshift field as a new way to extract cosmological information in the Universe. This new probe $\delta z (\hat{\mathbf {n}})$ consists of the statistics of sky maps built by projecting redshifts under a Gaussian window of width σz centred upon a redshift zobs, and weighted by the galaxy density field. We compute the angular power spectrum of the $\delta z (\hat{\mathbf {n}})$ field in both numerical simulations and in linear perturbation theory. From these, we find that the $\delta z (\hat{\mathbf {n}})$ field (i) is sensitive to the underlying density and peculiar velocity fields; (ii) is highly correlated, at the $\gtrsim 60\, {{\ \rm per\ cent}}$ level, to the line-of-sight projected peculiar velocity field; (iii) for narrow windows (σz < 0.03), it is almost completely uncorrelated to the projected galaxy angular density field under the same redshift window; and (iv) it is largely unaffected by multiplicative and additive systematic errors on the observed number of galaxies that are redshift-independent over ∼σz. We conclude that $\delta z (\hat{\mathbf {n}})$ is a simple and robust tomographic measure of the cosmic density and velocity fields, complementary to angular clustering, that will contribute to more complete exploitations of current and upcoming galaxy redshift surveys.
FlyRNAi.org—the database of the Drosophila RNAi screening center and transgenic RNAi project: 2021 update
Authors: Hu Yanhui , Comjean Aram , Rodiger Jonathan , Liu Yifang , Gao Yue , Chung Verena , Zirin Jonathan , Perrimon Norbert , Mohr Stephanie E
Published: October 2020

The FlyRNAi database at the Drosophila RNAi Screening Center and Transgenic RNAi Project (DRSC/TRiP) provides a suite of online resources that facilitate functional genomics studies with a special emphasis on Drosophila melanogaster. Currently, the database provides: gene-centric resources that facilitate ortholog mapping and mining of information about orthologs in common genetic model species; reagent-centric resources that help researchers identify RNAi and CRISPR sgRNA reagents or designs; and data-centric resources that facilitate visualization and mining of transcriptomics data, protein modification data, protein interactions, and more. Here, we discuss updated and new features that help biological and biomedical researchers efficiently identify, visualize, analyze, and integrate information and data for Drosophila and other species. Together, these resources facilitate multiple steps in functional genomics workflows, from building gene and reagent lists to management, analysis, and integration of data.
HeRA: an atlas of enhancer RNAs across human tissues
Authors: Zhang Zhao , Hong Wei , Ruan Hang , Jing Ying , Li Shengli , Liu Yaoming , Wang Jun , Li Wenbo , Diao Lixia , Han Leng
Published: October 2020

Enhancer RNA (eRNA) is a type of long non-coding RNA transcribed from DNA enhancer regions. Despite critical roles of eRNA in gene regulation, the expression landscape of eRNAs in normal human tissue remains unexplored. Using numerous samples from the Genotype-Tissue Expression project, we characterized 45 411 detectable eRNAs and identified tens of thousands of associations between eRNAs and traits, including gender, race, and age. We constructed a co-expression network to identify millions of putative eRNA regulators and target genes across different tissues. We further constructed a user-friendly data portal, Human enhancer RNA Atlas (HeRA, https://hanlab.uth.edu/HeRA/). In HeRA, users can search, browse, and download the eRNA expression profile, trait-related eRNAs, and eRNA co-expression network by searching the eRNA ID, gene symbol, and genomic region in one or multiple tissues. HeRA is the first data portal to characterize eRNAs from 9577 samples across 54 human tissues and facilitates functional and mechanistic investigations of eRNAs.
Bilateral Deep Brain Stimulation is the Procedure to Beat for Advanced Parkinson Disease: A Meta-Analytic, Cost-Effective Threshold Analysis for Focused Ultrasound
Authors: Mahajan Uma V , Ravikumar Vinod K , Kumar Kevin K , Ku Seul , Ojukwu Disep I , Kilbane Camilla , Ghanouni Pejman , Rosenow Joshua M , Stein Sherman C , Halpern Casey H
Published: October 2020

BACKGROUND

Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective.

OBJECTIVE

To (1) quantify the utility (functional disability metric) imparted by DBS and radiofrequency ablation (RF), (2) compare cost-effectiveness of DBS and RF, and (3) establish a preliminary success threshold at which FUS would be cost-effective compared to these procedures.

METHODS

We performed a meta-analysis of articles (1998-2018) of DBS and RF targeting the globus pallidus or subthalamic nucleus in PD patients and calculated utility using pooled Unified Parkinson Disease Rating Scale motor (UPDRS-3) scores and adverse events incidences. We calculated Medicare reimbursements for each treatment as a proxy for societal cost.

RESULTS

Over a 22-mo mean follow-up period, bilateral DBS imparted the most utility (0.423 quality-adjusted life-years added) compared to (in order of best to worst) bilateral RF, unilateral DBS, and unilateral RF, and was the most cost-effective (expected cost: $32 095 ± $594) over a 22-mo mean follow-up. Based on this benchmark, FUS would need to impart UPDRS-3 reductions of ∼16% and ∼33% to be the most cost-effective treatment over 2- and 5-yr periods, respectively.

CONCLUSION

Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS’s cost-effectiveness from a societal cost perspective.
Predicting Inpatient Mortality Among Encephalitis Patients: A Novel Admission Risk Score
Authors: Hansen Michael A , Samannodi Mohammed S , Hasbun Rodrigo
Published: October 2020

Background

Identifying underlying commonalities among all-cause encephalitis cases can be extraordinarily useful in predicting meaningful risk factors associated with inpatient mortality.

Methods

A retrospective cohort of patients with encephalitis was derived from a clinical chart review of adult patients (age ≥18 years) across 16 different hospitals in Houston, Texas, between January 2005 and July 2015. Clinical features at admission were assessed for their correlation with inpatient mortality and used to derive a final risk score prediction tool.

Results

The study included a total of 273 adult patients with all-cause encephalitis, 27 (9.9%) of whom died during hospitalization. A limited number of clinical features were substantially different between patients who survived and those who died (Charlson score, Glasgow coma scale [GCS], immunosuppression, fever on admission, multiple serologic studies, and abnormal imaging). A final multivariable logistic model was derived with the following risk factors, which were transformed into a scoring system: 1 point was assigned to the presence of a Charlson score >2, thrombocytopenia, or cerebral edema, and 2 points for a GCS value <8. Patients were then classified into different risk groups for inpatient mortality: 0 points (0%), 1 point (7%), 2 points (10.9%), 3 points (36.8%), and ≥4 points (81.8%).

Conclusions

The risk score developed from this study shows a high predictive value. This can be highly beneficial in alerting care providers to key clinical risk factors associated with in-hospital mortality in adults with encephalitis.
Onyx Embolization of Carotid-Cavernous Fistulas and Its Impact on Intraocular Pressure and Recurrence: A Case Series
Authors: Al Saiegh Fadi , Baldassari Michael P , Sweid Ahmad , Bilyk Jurij , Mouchtouris Nikolaos , Hafazalla Karim , Abendroth Michael , Velagapudi Lohit , Khanna Omaditya , Chalouhi Nohra , Sajja Kalyan , Tjoumakaris Stavropoula , Gooch M Reid , Rosenwasser Robert , Jabbour Pascal
Published: October 2020

BACKGROUND

Carotid-cavernous fistulas (CCFs) are acquired pathological shunting lesions between the carotid artery and the cavernous sinus leading to elevated intraocular pressure (IOP). CCFs are commonly treated via endovascular embolization, which theoretically restores physiological pressure differentials.

OBJECTIVE

To present our institutional data with CCF treated with embolization and discuss endovascular routes, recurrence rates, and dynamic IOP changes.

METHODS

Retrospective analysis of 42 CCF patients who underwent Onyx (Covidien, Irvine, California) embolization and pre- and postoperative IOP measurement at a single institution.

RESULTS

CCFs were 19.0% direct (type A) and 81.0% indirect (types B, C, or D). Onyx-18 liquid embolisate was used during all embolizations. Overall rate of total occlusion was 83.3% and was statistically similar between direct and indirect fistulas. Preoperative IOP was elevated in 37.5%, 100.0%, 75.0%, and 50% in type A, B, C, and D fistulas, respectively. Average ΔIOP was −7.3 ± 8.5 mmHg (range: −33 to +8). Follow-up time was 4.64 ± 7.62 mo. Full angiographic occlusion was a predictor of symptom resolution at 1 mo (P = .026) and 6 mo (P = .021). Partial occlusion was associated with persistent symptoms postoperatively at 1 mo (P = .038) and 6 mo follow-up (P = .012). Beyond 6 mo, negative ΔIOP was associated with continued symptom improvement. Recurrence occurred in 9.5% of patients, all of which were indirect CCFs.

CONCLUSION

Onyx embolization of CCF is an effective treatment for CCF and often results in the reversal of IOP elevation. Full occlusion predicts favorable clinical outcomes up to 6 mo. Postoperative IOP reduction may indicate favorable long-term clinical outcomes.
Looking at shadows of entanglement wedges
Authors: Kusuki Yuya , Suzuki Yuki , Takayanagi Tadashi , Umemoto Koji
Published: October 2020

We present a new method of deriving shapes of entanglement wedges directly from conformal field theory (CFT) calculations. We point out that a reduced density matrix in holographic CFTs possesses a sharp wedge structure such that inside the wedge we can distinguish two local excitations, while outside we cannot. We can determine this wedge, which we call a CFT wedge, by computing a distinguishability measure. We find that CFT wedges defined by the fidelity or Bures distance as a distinguishability measure coincide perfectly with shadows of entanglement wedges in anti-de Sitter (AdS)/CFT. We confirm this agreement between CFT wedges and entanglement wedges for two-dimensional holographic CFTs where the subsystem is chosen to be an interval or double intervals, as well as higher-dimensional CFTs with a round ball subsystem. On the other hand, if we consider a free scalar CFT, we find that there are no sharp CFT wedges. This shows that sharp entanglement wedges emerge only for holographic CFTs owing to the large-$N$ factorization. We also generalize our analysis to a time-dependent example and to a holographic boundary conformal field theory (AdS/BCFT). Finally, we study other distinguishability measures to define CFT wedges. We observe that some of the measures lead to CFT wedges which slightly deviate from the entanglement wedges in AdS/CFT, and we give a heuristic explanation for this. This paper is an extended version of our earlier letter (arXiv:1908.09939 [hep-th]) and includes various new observations and examples.
The risks of major cardiac events among patients with psoriatic arthritis treated with apremilast, biologics, DMARDs or corticosteroids
Authors: Persson Rebecca , Hagberg Katrina Wilcox , Qian Yiran , Vasilakis-Scaramozza Catherine , Jick Susan
Published: October 2020

Objectives

People with PsA are at increased risk of cardiovascular disease. The objective of this study was to quantify the risk of myocardial infarction (MI), stroke and revascularizations in people with apremilast-treated PsA compared with patients receiving other PsA treatments.

Methods

We conducted a cohort study of 68 678 patients with PsA treated with apremilast, TNF inhibitor (TNF-i) biologics, IL-17 or -12/23 biologics, conventional DMARDs or CS in the United States MarketScan database. Cohort entry was date of first study drug after 21 March 2014. Cases were patients with MI, stroke or revascularization. We calculated incidence rates (IRs) and incidence rate ratios for each outcome by exposure.

Results

We identified 292 MI, 151 stroke and 475 revascularizations cases. IRs for MI were lowest for users of TNF-i biologics [1.4 per 1000 person-years (PY)] and similar for all other treatments, including apremilast, ranging from 1.8 to 3.8 per 1000 PY. IRs were similar for all treatments for both stroke (0.1–1.6 per 1000 PY) and revascularization (3.1–5.1 per 1000 PY). IRs for apremilast were 2.5 per 1000 PY for MI, 1.6 per 1000 PY for stroke and 3.3 per 1000 PY for revascularization.

Conclusion

In patients with treated PsA, IRs of MI, stroke and revascularization were low for all systemic treatments evaluated. Although the number of events was small, apremilast exposure did not signal potential acute cardiovascular harm and was not associated with a material increase in the risk of these serious cardiac events.
HyPyP: a Hyperscanning Python Pipeline for inter-brain connectivity analysis
Authors: Ayrolles Anaël , Brun Florence , Chen Phoebe , Djalovski Amir , Beauxis Yann , Delorme Richard , Bourgeron Thomas , Dikker Suzanne , Dumas Guillaume
Published: October 2020

The bulk of social neuroscience takes a ‘stimulus-brain’ approach, typically comparing brain responses to different types of social stimuli, but most of the time in the absence of direct social interaction. Over the last two decades, a growing number of researchers have adopted a ‘brain-to-brain’ approach, exploring similarities between brain patterns across participants as a novel way to gain insight into the social brain. This methodological shift has facilitated the introduction of naturalistic social stimuli into the study design (e.g. movies) and, crucially, has spurred the development of new tools to directly study social interaction, both in controlled experimental settings and in more ecologically valid environments. Specifically, ‘hyperscanning’ setups, which allow the simultaneous recording of brain activity from two or more individuals during social tasks, has gained popularity in recent years. However, currently, there is no agreed-upon approach to carry out such ‘inter-brain connectivity analysis’, resulting in a scattered landscape of analysis techniques. To accommodate a growing demand to standardize analysis approaches in this fast-growing research field, we have developed Hyperscanning Python Pipeline, a comprehensive and easy open-source software package that allows (social) neuroscientists to carry-out and to interpret inter-brain connectivity analyses.
Mind the Outgroup and Bare Branches in Total-Evidence Dating: a Case Study of Pimpliform Darwin Wasps (Hymenoptera, Ichneumonidae)
Authors: Spasojevic Tamara , Broad Gavin R , Sääksjärvi Ilari E , Schwarz Martin , Ito Masato , Korenko Stanislav , Klopfstein Seraina
Published: October 2020

Taxon sampling is a central aspect of phylogenetic study design, but it has received limited attention in the context of total-evidence dating, a widely used dating approach that directly integrates molecular and morphological information from extant and fossil taxa. We here assess the impact of commonly employed outgroup sampling schemes and missing morphological data in extant taxa on age estimates in a total-evidence dating analysis under the uniform tree prior. Our study group is Pimpliformes, a highly diverse, rapidly radiating group of parasitoid wasps of the family Ichneumonidae. We analyze a data set comprising 201 extant and 79 fossil taxa, including the oldest fossils of the family from the Early Cretaceous and the first unequivocal representatives of extant subfamilies from the mid-Paleogene. Based on newly compiled molecular data from ten nuclear genes and a morphological matrix that includes 222 characters, we show that age estimates become both older and less precise with the inclusion of more distant and more poorly sampled outgroups. These outgroups not only lack morphological and temporal information but also sit on long terminal branches and considerably increase the evolutionary rate heterogeneity. In addition, we discover an artifact that might be detrimental for total-evidence dating: “bare-branch attraction,” namely high attachment probabilities of certain fossils to terminal branches for which morphological data are missing. Using computer simulations, we confirm the generality of this phenomenon and show that a large phylogenetic distance to any of the extant taxa, rather than just older age, increases the risk of a fossil being misplaced due to bare-branch attraction. After restricting outgroup sampling and adding morphological data for the previously attracting, bare branches, we recover a Jurassic origin for Pimpliformes and Ichneumonidae. This first age estimate for the group not only suggests an older origin than previously thought but also that diversification of the crown group happened well before the Cretaceous-Paleogene boundary. Our case study demonstrates that in order to obtain robust age estimates, total-evidence dating studies need to be based on a thorough and balanced sampling of both extant and fossil taxa, with the aim of minimizing evolutionary rate heterogeneity and missing morphological information. [Bare-branch attraction; ichneumonids; fossils; morphological matrix; phylogeny; RoguePlots.]
Extensive genetic diversity and host range of rodent-borne coronaviruses
Authors: Wang Wen , Lin Xian-Dan , Zhang Hai-Lin , Wang Miao-Ruo , Guan Xiao-Qing , Holmes Edward C , Zhang Yong-Zhen
Published: October 2020

To better understand the genetic diversity, host associations and evolution of coronaviruses (CoVs) in China we analyzed a total of 696 rodents encompassing 16 different species sampled from Zhejiang and Yunnan provinces. Based on reverse transcriptase PCR-based CoV screening of fecal samples and subsequent sequence analysis of the RNA-dependent RNA polymerase gene, we identified CoVs in diverse rodent species, comprising Apodemus agrarius, Apodemus chevrieri, Apodemus latronum, Bandicota indica, Eothenomys cachinus, Eothenomys miletus, Rattus andamanensis, Rattus norvegicus, and Rattus tanezumi. CoVs were particularly commonplace in A. chevrieri, with a detection rate of 12.44 per cent (24/193). Genetic and phylogenetic analysis revealed the presence of three groups of CoVs carried by a range of rodents that were closely related to the Lucheng Rn rat CoV (LRNV), China Rattus CoV HKU24 (ChRCoV_HKU24), and Longquan Rl rat CoV (LRLV) identified previously. One newly identified A. chevrieri-associated virus closely related to LRNV lacked an NS2 gene. This virus had a similar genetic organization to AcCoV-JC34, recently discovered in the same rodent species in Yunnan, suggesting that it represents a new viral subtype. Notably, additional variants of LRNV were identified that contained putative non-structural (NS)2b genes located downstream of the NS2 gene that were likely derived from the host genome. Recombination events were also identified in the open reading frame (ORF) 1a gene of Lijiang-71. In sum, these data reveal the substantial genetic diversity and genomic complexity of rodent-borne CoVs, and extend our knowledge of these major wildlife virus reservoirs.
Nightshade Curly Top Virus: A Possible New Virus of the Genus Topocuvirus Infecting Solanum nigrum in China
Authors: Sun Kai , Liang Yan , Zhong Xueting , Hu Xuenan , Zhang Pengjun , Yu Xiaoping
Published: October 2020

Virus-like symptoms, including leaf deformation and curling, were observed on nightshade (Solanum nigrum) in Zhejiang Province, China. To identify possible pathogenic viruses or viroids, a symptomatic sample was subjected to deep sequencing of small interfering RNAs. Assembly of the resulting sequences led to identification of a novel geminivirus, provisionally designated nightshade curly top virus (NCTV). The complete genomic DNA sequence is 2,867 nucleotides and encodes seven open reading frames. NCTV shares 77.1% overall nucleotide sequence identity, 86.3% coat protein amino acid identity, and 78.9% replication-associated protein amino acid sequence identity with Tomato pseudo-curly top virus, a member of the genus Topocuvirus. PCR screening of nightshade field isolates indicated that NCTV is widely distributed in Zhejiang. Agrobacterium-mediated inoculation revealed that NCTV is highly infectious to Nicotiana benthamiana, S. nigrum, S. lycopersicum, and S. tuberosum. Based on pairwise comparisons and phylogenetic analyses, NCTV is proposed as a provisional member of the genus Topocuvirus.
Decontamination of Ceratocystis Pathogens Responsible for Rapid ʻŌhiʻa Death
Authors: Roy Kylle , Jaenecke Kelly A. , Bjontegard Nikko , Mikros Dan , Dunkle Ellen J. , Yanger Corie , Sugiyama Lionel S. , Keith Lisa M. , Peck Robert W.
Published: October 2020

Rapid ʻōhiʻa death (ROD) is caused by two recently described species of Ceratocystis, C. lukuohia and C. huliohia. These fungi are decimating ʻōhiʻa lehua (Metrosideros polymorpha), the keystone native tree species of Hawaiʻi. Viable Ceratocystis propagules can persist in ambrosia beetle frass (Coleoptera: Scolytinae), and movement of the frass may play a key role in the spread of the disease. In order to prevent the spread of ROD, we developed effective and practical surface (e.g., tools and shoes) decontamination methods to be used by researchers, managers, and the public alike. We first tested different household and laboratory disinfectants on the Ceratocystis fungi in culture, and then we applied the effective culture disinfectants to contaminated ambrosia beetle frass. Laboratory-grade ethanol (70, 80, and 95%), Clorox bleach (10%, 0.825% active ingredient [a.i.]), and isopropanol (70 and 91%), were all equally effective at decontaminating cultured C. lukuohia and C. huliohia. Although all concentrations of isopropanol (50, 70, and 90%) and ethanol (50, 70, and 90%) were effective disinfectants of Ceratocystis-contaminated frass, treatments of frass with up to 20% Clorox bleach (1.2% a.i.) were not completely adequate at killing the fungus. These data reveal that bleach is not a sufficient ROD disinfectant when frass is present, and isopropanol or ethanol are the more reliable options.
Genome Analysis of Two Newly Emerged Potato Late Blight Isolates Sheds Light on Pathogen Adaptation and Provides Tools for Disease Management
Authors: Zhang Fan , Chen Han , Zhang Xinjie , Gao Chuyun , Huang Jie , Lü Li , Shen Danyu , Wang Luyao , Huang Chong , Ye Wenwu , Zheng Xiaobo , Wang Yuanchao , Vossen Jack H. , Dong Suomeng
Published: October 2020

Phytophthora infestans, the causal agent of the Irish Potato Famine in the 1840s, is one of the most destructive crop pathogens that threaten global food security. Host resistance (R) genes may help to control the disease, but recognition by through the gene products can be evaded by newly emerging isolates. Such isolates are dangerous as they may cause disease outbreaks under favorable conditions. However, our lack of knowledge about adaptation in these isolates jeopardizes an apt response to resistance breakdown. Here we performed genome and transcriptome sequencing of HB1501 and HN1602, two field isolates from distinct Chinese geographic regions. We found extensive polymorphisms in these isolates, including gene copy number variations, nucleotide polymorphisms, and gene expression changes. Effector encoding genes, which contribute to virulence, show distinct expression landscapes in P. infestans isolates HB1501 and HN1602. In particular, polymorphisms at multiple effectors required for recognition (Avr loci) enabled these isolates to overcome corresponding R gene based resistance. Although the isolates evolved multiple strategies to evade recognition, we experimentally verified that several R genes such as R8, RB, and Rpi-vnt1.1 remain effective against these isolates and are valuable to potato breeding in the future. In summary, rapid characterization of the adaptation in emerging field isolates through genomic tools inform rational agricultural management to prevent potential future epidemics.
Investigation of an Outcomes-Driven, Computer-Assisted Approach to CI Fitting in Newly Implanted Patients
Authors: Zwolan Teresa A. , Presley Regina , Chenier Laura , Buck Barbara
Published: October 2020

Objective:

To evaluate the efficacy of outcomes received by newly implanted cochlear implant recipients when an outcomes-driven, computer-assisted approach to cochlear implantation fitting was used. This approach, referred to as “Fitting to Outcome eXpert,” or FOX, was developed by Otoconsult in Antwerp, Belgium.

Design:

Thirty-one newly implanted subjects participated in a nonrandomized, single-subject, repeated measures design that involved a within-subject comparison of preoperative and postoperative speech recognition scores. Sound processors for all subjects were programmed using the FOX software that utilized the evidence-based results of various psychoacoustic tests to adjust MAP parameters and improve performance. Additionally, mean word and sentence recognition scores obtained by the subjects programmed with FOX were compared to results obtained by newly implanted patients enrolled in the Nucleus CI532 clinical trial whose devices were programmed using traditional methods.

Results:

Subjects whose sound processors were programmed using FOX obtained a mean 6-month postactivation Consonant Nucleus Consonant word score of 60.2% correct. This represented an improvement of 46% age points when mean preactivation and postactivation scores were compared and represented a statistically significant change in score (p < 0.001). This mean score is similar to the mean 6-month Consonant Nucleus Consonant Word score of 61% obtained by 96 subjects enrolled in the Nucleus CI532 trial. Additionally, subjects in this study obtained a mean 6-month postactivation AzBio Sentence score of 42.7% correct when stimuli were presented at 65 dBA using a +10 signal-to-noise ratio. This score is also similar to the mean score of 43% obtained by 96 subjects enrolled in the Nucleus CI532 trial using the same test material and signal-to-noise ratio. Patients enrolled in this study attended 43% fewer programming appointments than the number reported by cochlear implantation centers in recent surveys of clinical care.

Conclusion:

The results of this study support the use of an outcomes-driven, computer-assisted approach to supplement the management of newly implanted cochlear implant recipients. Subjects whose devices were programmed using such an approach demonstrated mean postoperative word in quiet and sentence in noise scores comparable to those obtained by subjects in the Nucleus CI532 clinical trial whose devices were programmed using traditional programming techniques. Use of this approach positively impacted patient care by reducing the number of postoperative visits needed to optimize sound processor programs, simplified patient testing via the use of direct streaming, and ensured that patients received consistent programming of their sound processor, regardless of the location where the programming was performed.
The Cost of Intrinsic and Extrinsic Cognitive Demands on Auditory Functioning in Older Adults With Normal Hearing or Using Hearing Aids
Authors: Devesse Annelies , van Wieringen Astrid , Wouters Jan
Published: October 2020

Objectives:

We investigated the impact of both intrinsic and extrinsic cognitive demands on auditory and secondary task performance in older adults with normal hearing (NH) and adults using hearing aids (HAs) in an ecologically relevant listening environment.

Design:

Fifteen adults with NH and 15 adults using HAs (60 to 72 years of age) were recruited to perform the “Audiovisual True-to-Life Assessment of Auditory Rehabilitation”-paradigm (AVATAR), which combines an auditory-visual speech-in-noise task with three secondary tasks on either auditory localization or visual short-term memory in a preload multitask paradigm. Intrinsic demands were altered by presenting speech either at equivalent speech accuracy levels of 50% correct (SPIN50%) or equivalent speech-to-noise ratios of +5dB SNR (SPIN+5dB). We manipulated the amount of extrinsic cognitive demands by including one (dual condition) or three secondary tasks (quadruple condition). Performance decrements on the secondary tasks were considered to reflect an increase in resource allocation to speech understanding and thus an increase in listening effort. In addition, we administered a cognitive test battery as well as a questionnaire on self-reported hearing difficulties and subjective measures of effort and motivation.

Results:

Speech understanding and secondary task performance on the visual short-term memory task were lower in the SPIN50% condition compared to SPIN+5dB. Whereas speech understanding at SPIN50% was equally high in the dual and quadruple conditions, the quadruple condition resulted in lower secondary task performance on the visual short-term memory task, higher levels of self-reported effort, and lower motivation compared to the dual-task condition. The same was true for experimental conditions at SPIN+5dB. Additionally, adults with NH outperformed adults using HAs on speech understanding, auditory localization, and self-reported hearing abilities, but no group differences were observed on secondary task costs or cognitive measures.

Conclusions:

This study showed that, irrespective of the hearing status of the listener, speech performance was not affected by the amount of extrinsic cognitive demands, but was worse and required more effort under conditions with a more negative SNR. Also, increasing the extrinsic cognitive demands resulted in lower performance on one of the secondary tasks, suggesting that more complex listening environments require more effort. Although adults with NH outperformed HA users on speech understanding and auditory localization, the two groups did not differ with respect to secondary task costs.
Extracorporeal Carbon Dioxide Removal in the Treatment of Status Asthmaticus
Authors: Bromberger Bianca J. , Agerstrand Cara , Abrams Darryl , Serra Alexis , Apsel Dana , Tipograf Yuliya , Ginsburg Mark E. , Ebright Michael I. , Stanifer B. Payne , Oommen Roy , Bacchetta Matthew , Brodie Daniel , Sonett Joshua R.
Published: October 2020

Objectives:

Venovenous extracorporeal carbon dioxide removal may be lifesaving in the setting of status asthmaticus.

Design:

Retrospective review.

Setting:

Medical ICU.

Patients:

Twenty-six adult patients with status asthmaticus treated with venovenous extracorporeal carbon dioxide removal.

Interventions:

None.

Measurements and Main Results:

Demographic data and characteristics of current and prior asthma treatments were obtained from the electronic medical record. Mechanical ventilator settings, arterial blood gases, vital signs, and use of vasopressors were collected from the closest time prior to cannulation and 24 hours after initiation of extracorporeal carbon dioxide removal. Extracorporeal carbon dioxide removal settings, including blood flow and sweep gas flow, were collected at 24 hours after initiation of extracorporeal carbon dioxide removal. Outcome measures included rates of survival to hospital discharge, ICU and hospital lengths of stay, duration of invasive mechanical ventilation and extracorporeal carbon dioxide removal support, and complications during extracorporeal carbon dioxide removal. Following the initiation of extracorporeal carbon dioxide removal, blood gas values were significantly improved at 24 hours, as were peak airway pressures, intrinsic positive end-expiratory pressure, and use of vasopressors. Survival to hospital discharge was 100%. Twenty patients (76.9%) were successfully extubated while receiving extracorporeal carbon dioxide removal support; none required reintubation. The most common complication was cannula-associated deep venous thrombosis (six patients, 23.1%). Four patients (15.4%) experienced bleeding that required a transfusion of packed RBCs.

Conclusions:

In the largest series to date, use of venovenous extracorporeal carbon dioxide removal in patients with status asthmaticus can provide a lifesaving means of support until the resolution of the exacerbation, with an acceptably low rate of complications. Early extubation in select patients receiving extracorporeal carbon dioxide removal is safe and feasible and avoids the deleterious effects of positive-pressure mechanical ventilation in this patient population.
Consumptive Coagulopathy Involving Amniotic Fluid Embolism: The Importance of Earlier Assessments for Interventions in Critical Care
Authors: Oda Tomoaki , Tamura Naoaki , Ide Rui , Itoh Toshiya , Horikoshi Yoshimasa , Matsumoto Masako , Narumi Megumi , Kohmura-Kobayashi Yukiko , Furuta-Isomura Naomi , Yaguchi Chizuko , Uchida Toshiyuki , Suzuki Kazunao , Itoh Hiroaki , Kanayama Naohiro
Published: October 2020

Objectives:

Amniotic fluid embolism is a rare disease that induces fatal coagulopathy; however, due to its rarity, it has not yet been examined in detail. The strict diagnostic criteria by Clark for amniotic fluid embolism include severe coagulopathy complicated by cardiopulmonary insufficiency, whereas the Japanese criteria also include postpartum hemorrhage or Disseminated Intravascular Coagulation in clinical practice. Amniotic fluid embolism cases with preceding consumptive coagulopathy may exist and are potential clinical targets for earlier assessments and interventions among amniotic fluid embolism cases fulfilling the Japanese, but not Clark criteria. The present study was performed to compare coagulopathy in the earlier stage between the amniotic fluid embolism patients diagnosed by Clark criteria (Clark group, n = 6), those by the Japanese criteria (Non-Clark group, n = 10), and peripartum controls and identify optimal clinical markers for earlier assessments of amniotic fluid embolism-related consumptive coagulopathy.

Design:

Retrospective case-control study.

Setting:

A single university-based center. Our amniotic fluid embolism registry program has accumulated clinical information and blood samples since 2003.

Patients:

Amniotic fluid embolism patients in the Clark and Non-Clark groups between 2009 and 2017 and peripartum controls.

Interventions:

None.

Measurements and Main Results:

Clinical information was collected on hemoglobin levels, platelet counts, and coagulation- and fibrinolysis-related variables. Fibrinolytic parameters were also measured and compared among the three groups before blood transfusion. Fibrinogen levels in all patients in the Clark group and most in the Non-Clark group decreased earlier than hemoglobin levels, which was consistent with the high hemoglobin/fibrinogen ratio and, thus, is a promising clinical marker for the earlier assessment of amniotic fluid embolism-related consumptive coagulopathy.

Conclusions:

Earlier evaluations of consumptive coagulopathy and hyperfibrinolysis using the hemoglobin/fibrinogen ratio following preemptive treatment may reduce the occurrence or prevent the aggravation of severe coagulopathy in amniotic fluid embolism patients.
Circadian Gene Expression Rhythms During Critical Illness
Authors: Maas Matthew B. , Iwanaszko Marta , Lizza Bryan D. , Reid Kathryn J. , Braun Rosemary I. , Zee Phyllis C.
Published: October 2020

Objectives:

Core clock genes regulate tissue-specific transcriptome oscillations that synchronize physiologic processes throughout the body, held in phase by the central circadian rhythm. The central circadian rhythm rapidly dampens with onset of critical illness, but the effect of critical illness on gene expression oscillations is unknown. The objective of this study was to characterize the rhythmicity and phase coherence of core clock genes and the broader transcriptome after onset of critical illness.

Design:

Cross-sectional study.

Setting:

ICUs and hospital clinical research unit.

Patients:

Critically ill patients within the first day of presenting from the community and healthy volunteers.

Interventions:

Usual care (critically ill patients) and modified constant routine (healthy volunteers).

Measurements and Main Results:

We studied 15 critically ill patients, including 10 with sepsis and five with intracerebral hemorrhage, and 11 healthy controls. The central circadian rhythm and rest-activity rhythms were profiled by continuous wrist actigraphy, and serum melatonin sampled every 2 hours along with whole blood for RNA isolation over 24 hours. The gene expression transcriptome was obtained by RNA sequencing. Core clock genes were analyzed for rhythmicity by cosinor fit. Significant circadian rhythmicity was identified in five of six core clock genes in healthy controls, but none in critically ill patients. TimeSignature, a validated algorithm based on 41 genes, was applied to assess overall transcriptome phase coherence. Median absolute error of TimeSignature was higher in individual critically ill patients than healthy patients (4.90 vs 1.48 hr) and was correlated with encephalopathy severity by Glasgow Coma Scale in critically ill patients (rho, –0.54; p = 0.036).

Conclusions:

Gene expression rhythms rapidly become abnormal during critical illness. The association between disrupted transcriptome rhythms and encephalopathy suggests a path for future work to elucidate the underlying pathophysiology.
State entropy and burst suppression ratio can show contradictory information
Authors: Georgii Marie-Therese , Pilge Stefanie , Schneider Gerhard , Kreuzer Matthias
Published: October 2020

BACKGROUND

Burst suppression is a characteristic electroencephalographic (EEG) pattern that reflects very deep levels of general anaesthesia and may correlate with increased risk of adverse outcomes such as postoperative delirium. EEG-based monitors such as the Entropy Module estimate the level of anaesthesia (state entropy) and provide another index reflecting the occurrence of burst suppression, that is the ratio of burst and suppression (BSR). In the Entropy Module, state entropy and BSR are not interconnected, as they are in the bispectral index (BIS). Hence, state entropy and BSR may provide contradicting information regarding the level of anaesthesia.

OBJECTIVES

We aimed to describe the frequency and characteristics of contradicting state entropy and BSR and to present possible strategies of how to act in these situations.

METHODS

We based our analyses on state entropy and BSR trend recordings from 2551 patients older than 59 years that showed BSR was > 0 throughout their intervention under general anaesthesia. We determined the maximum state entropy when BSR was > 0, the minimum state entropy with BSR = 0 and the duration of high state entropy with BSR > 0. Further, we selected four exemplar patients to present details of how state entropy and BSR can contradict each other during anaesthesia.

RESULTS

We observed a wide range of state entropy values with BSR > 0. The median [IQR] of the maximum state entropy with BSR > 0 was 53 [45 to 61] and the median of the minimum state entropy without BSR was 21 [15 to 26]. Contradictory BSR and state entropy could persist over several minutes. The presented cases highlight these contradictory BSR and state entropy situations.

CONCLUSIONS

Our results illustrate contradictory state entropy and BSR indices that may be relevant for anaesthesia navigation. Longer-lasting episodes may lead to incorrect titration of the depth of the hypnotic component of anaesthesia. Hence, our results demonstrate the necessity to monitor and check the raw EEG or EEG parameters that are less processed than the commercially available indices to safely navigate anaesthesia.
Calmodulinopathies: throwing back the veil on the newest life-threatening genetic arrhythmia syndrome
Authors: Etheridge Susan P. , Niu Mary C.
Published: October 2020

Purpose of review

This review provides a basic understanding of the calmodulin gene and its role in calcium homeostasis. We outline the functional effects and clinical expression of CALM mutations and review disease expression and management.

Recent findings

Calmodulinopathies are rare life-threatening arrhythmia syndromes affecting young individuals. They are caused by mutations in any of the three genes (CALM 1-3) that encode calmodulin (CaM), a ubiquitously expressed Ca

2+
signaling protein with multiple targets that in the heart, modulates several ion channels. Patients express varied phenotypes: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, sudden death, idiopathic ventricular fibrillation, hypertrophic cardiomyopathy, or mixed disease. This is severe disease. Over half of 2019 International Calmodulin Registry patients experienced recurrent cardiac events despite management strategies that included: monotherapy and combination therapy with beta blockers, sodium channel blockers, other antiarrhythmics, sympathetic denervation, and pacing. Induced pluripotent stem cell-derived cardiomyocytes from patients harboring CALM mutations have provided a platform for better understanding pathogenic mechanisms and avenues for therapy.

Calmodulinopathies are among the more novel inherited arrhythmia syndromes. These are rare but highly lethal diseases with diverse clinical expressions. The practicing electrophysiologist should be aware these conditions, how to recognize them clinically, and understand the challenges in management.
Endocrine-disrupting chemicals and breastfeeding duration: a review
Authors: Criswell Rachel , Crawford Kathryn A. , Bucinca Hana , Romano Megan E.
Published: October 2020

Purpose of review

The purpose of this review is to describe epidemiologic and toxicological literature investigating how endocrine-disrupting chemicals (EDCs) affect mammary gland development and function, thereby impacting lactation duration.

Recent findings

Perfluoroalkyl and polyfluoroalkyl substances appear to reduce breastfeeding duration through impaired mammary gland development, lactogenesis, and suppressed endocrine signaling. Halogenated aromatic hydrocarbons have differing associations with lactation duration, likely because of the variety of signaling pathways that they affect, pointing to the importance of complex mixtures in epidemiologic studies. Although epidemiologic literature suggests that pesticides and fungicides decrease or have no effect on lactation duration, toxicology literature suggests enhanced mammary gland development through estrogenic and/or antiandrogenic pathways. Toxicological studies suggest that phthalates may affect mammary gland development via estrogenic pathways but no association with lactation duration has been observed. Bisphenol A was associated with decreased duration of breastfeeding, likely through direct and indirect action on estrogenic pathways.

EDCs play a role in mammary gland development, function, and lactogenesis, which can affect breastfeeding duration. Further research should explore direct mechanisms of EDCs on lactation, the significance of toxicant mixtures, and transgenerational effects of EDCs on lactation.
The patient with irritable bowel syndrome-type symptoms: when to investigate and how?
Authors: Quigley Eamonn M.M.
Published: October 2020

Purpose of review

Irritable bowel syndrome (IBS) is a very common disorder whose clinical presentation varies considerably between patients as well as within the same individual over time. Many of its symptoms, such as pain, diarrhea, constipation and bloating, may be manifestations of a host of other gastrointestinal diseases; some accompanied by increased mortality. This presents the clinician with a real dilemma: how to sensibly investigate the patient in which one suspects IBS but there is a nagging doubt that ‘it could be something else’? Could one miss ‘something serious’? This short review attempts to provide both an evidence-based response to these vexing questions and a practical guide to detecting alternative diagnoses in the subject with IBS-type symptoms.

Recent findings

Clinical features, patient demographics and the clinical context can help to significantly narrow the differential diagnosis of the individual with IBS-type symptoms and may permit a positive diagnosis of IBS. The advent of noninvasive serological and stool tests has greatly facilitated differentiation from celiac disease and inflammatory bowel disease, respectively. In the older, female diarrhea sufferer microscopic colitis should be considered. The role of bile acid diarrhea in the individual with diarrhea-predominant IBS is emphasized; the status of small intestinal bacterial overgrowth in IBS remain uncertain.

Attention to detail in the clinical evaluation of the individual with IBS-like symptoms will facilitate a selective and targeted approach to investigation. Wherever indicated, widely available serological and fecal tests will serve to bolster the diagnosis by excluding other options. Proceeding to more invasive testing should be dictated by clinical presentation and scenario with the threshold for intervention being generally lower among those with prominent diarrhea.
Advances, gaps and opportunities in the detection of familial hypercholesterolemia: overview of current and future screening and detection methods
Authors: Ibrahim Shirin , Reeskamp Laurens F. , Stroes Erik S.G. , Watts Gerald F.
Published: October 2020

Purpose of review

Studies reaffirm that familial hypercholesterolemia is more prevalent than initially considered, with a population frequency of approximately one in 300. The majority of patients remains unidentified. This warrants critical evaluation of existing screening methods and exploration of novel methods of detection.

Recent findings

New public policy recommendations on the detection of familial hypercholesterolemia have been made by a global community of experts and advocates. Phenotypic tools for diagnosing index cases remain inaccurate. Genetic testing is the gold standard for familial hypercholesterolemia and a new international position statement has been published. Correction of LDL cholesterol (LDL-C) for the cholesterol content of lipoprotein(a) [Lp(a)] may increase the precision of the phenotypic diagnosis of familial hypercholesterolemia. Cascade cotesting for familial hypercholesterolemia and elevated Lp(a) levels provides a new opportunity to stratify risk in families. Digital technology and machine learning methods, coupled with clinical alert and decision support systems, lead the way in more efficient approaches for detecting and managing index cases. Universal screening of children, combined with child-parent cascade testing, appears to be the most effective method for underpinning a population strategy for maximizing the detection of familial hypercholesterolemia.

Detection of familial hypercholesterolemia can be enhanced by optimizing current diagnostic algorithms, probing electronic health records with novel information technologies and integrating universal screening of children with cascade testing of parents and other relatives.