bluuebunny/crossref_metadata_2025 huggingface dataset:
Astrometric requirements for strong lensing time-delay cosmography
Authors: Birrer Simon , Treu Tommaso
Published: August 2019

The time-delay between the arrival of photons of multiple images of time-variable sources can be used to constrain absolute distances in the Universe, and in turn obtain a direct estimate of the Hubble constant and other cosmological parameters. To convert the time-delay into distances, it is well known that the gravitational potential of the main deflector and the contribution of the matter along the line of sight need to be known to a sufficient level of precision. In this paper, we discuss a new astrometric requirement that is becoming important, as time-delay cosmography improves in precision and accuracy with larger samples, and better data and modelling techniques. We derive an analytic expression for the propagation of astrometric uncertainties on the multiple image positions into the inference of the Hubble constant and derive requirements depending on image separation and relative time-delay. We note that this requirement applies equally to the image position measurements and to the accuracy of the model in reproducing them. To illustrate the requirement, we discuss some example lensing configurations and highlight that, especially for time-delays of order 10 d or shorter, the relative astrometric requirement is of order milliarcseconds, setting a tight requirement on both measurements and models. With current optical infrared technology, astrometric uncertainties may be the dominant limitation for strong lensing cosmography in the small image-separation regime when high-precision time-delays become accessible.
Molecular characteristics of reiterative DNA unwinding by the Caenorhabditis elegans RecQ helicase
Authors: Choi Seoyun , Lee Seung-Won , Kim Hajin , Ahn Byungchan
Published: August 2019

The RecQ family of helicases is highly conserved both structurally and functionally from bacteria to humans. Defects in human RecQ helicases are associated with genetic diseases that are characterized by cancer predisposition and/or premature aging. RecQ proteins exhibit 3′-5′ helicase activity and play critical roles in genome maintenance. Recent advances in single-molecule techniques have revealed the reiterative unwinding behavior of RecQ helicases. However, the molecular mechanisms involved in this process remain unclear, with contradicting reports. Here, we characterized the unwinding dynamics of the Caenorhabditis elegans RecQ helicase HIM-6 using single-molecule fluorescence resonance energy transfer measurements. We found that HIM-6 exhibits reiterative DNA unwinding and the length of DNA unwound by the helicase is sharply defined at 25–31 bp. Experiments using various DNA substrates revealed that HIM-6 utilizes the mode of ‘sliding back’ on the translocated strand, without strand-switching for rewinding. Furthermore, we found that Caenorhabditis elegans replication protein A, a single-stranded DNA binding protein, suppresses the reiterative behavior of HIM-6 and induces unidirectional, processive unwinding, possibly through a direct interaction between the proteins. Our findings shed new light on the mechanism of DNA unwinding by RecQ family helicases and their co-operation with RPA in processing DNA.
DNA Analysis by Restriction Enzyme (DARE) enables concurrent genomic and epigenomic characterization of single cells
Authors: Viswanathan Ramya , Cheruba Elsie , Cheow Lih Feng
Published: August 2019

Genome-wide profiling of copy number alterations and DNA methylation in single cells could enable detailed investigation into the genomic and epigenomic heterogeneity of complex cell populations. However, current methods to do this require complex sample processing and cleanup steps, lack consistency, or are biased in their genomic representation. Here, we describe a novel single-tube enzymatic method, DNA Analysis by Restriction Enzyme (DARE), to perform deterministic whole genome amplification while preserving DNA methylation information. This method was evaluated on low amounts of DNA and single cells, and provides accurate copy number aberration calling and representative DNA methylation measurement across the whole genome. Single-cell DARE is an attractive and scalable approach for concurrent genomic and epigenomic characterization of cells in a heterogeneous population.
The Efficacy of Ultrasonic Bone Scalpel for Unilateral Cervical Open-Door Laminoplasty: A Randomized Controlled Trial
Authors: Kim Chi Heon , Chung Chun Kee , Choi Yunhee , Kuo Calvin C , Lee Urim , Yang Seung Heon , Lee Chang-Hyun , Jung Jong-Myung , Hwang Sung Hwan , Kim Dong Hwan , Yoon Joon Ho , Paik Seoi , Lee Hwa Jin , Jung Sunhyang , Park Sung Bae , Kim Kyoung-Tae , Park Hee-Pyoung
Published: August 2019

BACKGROUND

In cervical open-door laminoplasty for cervical myelopathy, a high-speed rotatory drill and rongeurs are used to make unicortical troughs and bicortical openings in the laminae. The lamina is reflected at the trough to enlarge the spinal canal, followed by bone healing on the hinge side to stabilize laminoplasty. The ultrasonic bone scalpel (UBS) has been used due to theoretical advantages including a better hinge union rate, less soft tissue trauma, less neurological injury, and shorter operative time.

OBJECTIVE

To assess the superiority of UBS for hinge union compared to the drill through randomized controlled trial.

METHODS

In 190 randomly allocated cervical myelopathy patients, the trough and opening at the lamina were made using either the drill (n = 95) or UBS (n = 95) during 2015 to 2018. The primary outcome was the hinge union rate on 6-mo postoperative computed tomography. Secondary outcomes included the hinge union rate at 12 mo, the operative time, intraoperative/postoperative bleeding, neurological injury, complications, and clinical outcomes over a 24-mo follow-up.

RESULTS

Hinge union in all laminae was achieved in 60.0% (drill) and 43.9% (UBS) of patients at 6 mo (intention-to-treat analysis; P = .02; odds ratio, 2.1) and in 91.9% (drill) and 86.5% (UBS) at 12 mo. Dural injury only occurred in the drill group (2.1%), and the UBS group showed significantly less intraoperative bleeding (P < .01). The other secondary outcomes did not differ between groups.

CONCLUSION

The hinge union rate was inferior in the UBS group at 6 mo postoperatively, but UBS was efficacious in reducing dural injuries and bleeding.
Asking the Right Questions About Secondhand Smoke
Authors: Klein Jonathan D , Chamberlin Margaret E , Kress Elizabeth A , Geraci Mark W , Rosenblatt Susan , Boykan Rachel , Jenssen Brian , Rosenblatt Stanley M , Milberger Sharon , Adams William G , Goldstein Adam O , Rigotti Nancy A , Hovell Melbourne F , Holm Amanda L , Vandivier Richard W , Croxton Thomas L , Young Patricia L , Blissard Lani , Jewell Kate , Richardson Leisa , Ostrow John , Resnick Elissa A
Published: August 2019

Introduction

Despite knowledge about major health effects of secondhand tobacco smoke (SHS) exposure, systematic incorporation of SHS screening and counseling in clinical settings has not occurred.

Methods

A three-round modified Delphi Panel of tobacco control experts was convened to build consensus on the screening questions that should be asked and identify opportunities and barriers to SHS exposure screening and counseling. The panel considered four questions: (1) what questions should be asked about SHS exposure; (2) what are the top priorities to advance the goal of ensuring that these questions are asked; (3) what are the barriers to achieving these goals; and (4) how might these barriers be overcome. Each panel member submitted answers to the questions. Responses were summarized and successive rounds were reviewed by panel members for consolidation and prioritization.

Results

Panelists agreed that both adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from any tobacco products in their usual environment. The panel found that consistent clinician training, quality measurement or other accountability, and policy and electronic health records interventions were needed to successfully implement consistent screening.

Conclusions

The panel successfully generated screening questions and identified priorities to improve SHS exposure screening. Policy interventions and stakeholder engagement are needed to overcome barriers to implementing effective SHS screening.

Implications

In a modified Delphi panel, tobacco control and clinical prevention experts agreed that all adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from tobacco products. Consistent training, accountability, and policy and electronic health records interventions are needed to implement consistent screening. Increasing SHS screening will have a significant impact on public health and costs.
Social Causation, Social Selection, or Common Determinants? Examining Competing Explanations for the Link Between Young Adult Unemployment and Nicotine Dependence
Authors: Lee Jungeun Olivia , Horwood L John , Lee Woo Jung , Hackman Daniel A , McLeod Geraldine Fh , Boden Joseph M
Published: August 2019

Introduction

Unemployment has been related to smoking, yet the causal nature of the association is subject to continued debate. Social causation argues that unemployment triggers changes in smoking, whereas the social selection hypothesis proposes that pre-existing smoking behavior lowers the probability of maintaining employment. The present study tested these competing explanations while accounting for another alternative explanation—common liability.

Methods

Data were from the Christchurch Health and Development Study, a longitudinal cohort followed from birth to age 35. Odds were generated for having nicotine dependence in models for social causation and being unemployed in models for social selection. These models were extended to include possible common liability factors during childhood (eg, novelty seeking) and young adulthood (eg, major depression).

Results

In the model testing social causation, coefficients representing the impacts of unemployment on nicotine dependence remained statistically significant and robust (odds ratio [OR] = 1.55; 95% confidence interval [CI] = 1.20, 2.00), even after accounting for common determinant measures. In contrast, a reverse social selection model revealed that coefficients representing the impacts of nicotine dependence on unemployment substantially attenuated and became statistically nonsignificant as childhood factors were added (OR = 1.14; 95% CI = 0.90, 1.45).

Conclusions

Unemployment may serve as inroads to nicotine addiction among young adults, not the other way, even in the context of nicotine dependence, a more impaired form of smoking that may arguably hold higher potential to generate social selection processes. This social causation process cannot be completely attributable to common determinant factors.

Implications

It is critical to clarify whether unemployment triggers changes in smoking behaviors (ie, social causation) or vice versa (ie, social selection)—the answers to the question will lead to public health strategies with very different intervention targets to break the linkage. The current study findings favor social causation over social selection, regardless of gender, and support a needed shift in service profiles for unemployed young adults—from a narrow focus on job skills training to a more holistic approach that incorporates knowledge from addiction science in which unemployed young adults can find needed services to cope with job loss.
An Increase in the Tobacco Age-of-Sale to 21: For Debate in Europe
Authors: Nuyts Paulien A W , Kuipers Mirte A G , Willemsen Marc C , Kunst Anton E
Published: August 2019

Implications

A debate on the adoption of a tobacco age-of-sale of 21 in Europe has not occurred, with the recent exception of the United Kingdom. The current legally set age of 18 years is proving to be inadequate as adolescents continue to access cigarettes. Tobacco 21 laws have the potential to further limit access to cigarettes by minors. We believe that soon the time will be ripe for this discussion to spread throughout Europe, specifically among countries that have adopted a smoke-free generation movement.
The whole picture of the large-scale structure of the CL1604 supercluster at z ∼ 0.9
Authors: Hayashi Masao , Koyama Yusei , Kodama Tadayuki , Komiyama Yutaka , Lin Yen-Ting , Miyazaki Satoshi , Shimakawa Rhythm , Suzuki Tomoko L , Tanaka Ichi , Yamamoto Moegi , Yamamoto Naoaki
Published: August 2019

We present the large-scale structure over a more than 50 comoving Mpc scale at $z \sim 0.9$ where the CL1604 supercluster, which is one of the largest structures ever known at high redshifts, is embedded. The wide-field deep imaging survey by the Subaru Strategic Program with the Hyper Suprime-Cam reveals that the already-known CL1604 supercluster is a mere part of larger-scale structure extending to both the north and the south. We confirm that there are galaxy clusters at three slightly different redshifts in the northern and southern sides of the supercluster by determining the redshifts of 55 red-sequence galaxies and 82 star-forming galaxies in total via follow-up spectroscopy with Subaru/FOCAS and Gemini-N/GMOS. This suggests that the structure known as the CL1604 supercluster is the tip of the iceberg. We investigate the stellar population of the red-sequence galaxies using 4000 Å break and Balmer H$\delta$ absorption lines. Almost all of the red-sequence galaxies brighter than $21.5\:$mag in the z band show an old stellar population of $\gtrsim\! 2\:$Gyr. The comparison of composite spectra of the red-sequence galaxies in the individual clusters show that the galaxies at a similar redshift have a similar stellar population age, even if they are located $\sim\! 50\:$Mpc apart from each other. However, there could be a large variation in the star formation history. Therefore, it is likely that galaxies associated with the large-scale structure on a 50 Mpc scale formed at almost the same time, have assembled into the denser regions, and then have evolved with different star formation history along the hierarchical growth of the cosmic web.
Why Special Relativity is a Problem for the A-Theory
Authors: Turner Jason
Published: August 2019

Neither special nor general relativity make any use of a notion of absolute simultaneity. Since A-Theories about time do make use of such a notion, it is natural to suspect that relativity and A-Theory are inconsistent. Many authors have argued that they are in fact not inconsistent, and I agree with that diagnosis here. But that doesn’t mean, as these authors seem to think, that A-Theory and relativity are happy bedfellows. I argue that relativity gives us good reason to reject the A-Theory, even though strict inconsistency isn’t that reason.
Fermion mass hierarchy in grand gauge-Higgs unification
Authors: Maru Nobuhito , Yatagai Yoshiki
Published: August 2019

Grand gauge-Higgs unification of 5D $SU(6)$ gauge theory on an orbifold $S^1/Z_2$ is discussed. The Standard Model (SM) fermions are introduced on one of the boundaries and some massive bulk fields are also introduced so that they couple to the SM fermions through the mass terms on the boundary. Integrating out the bulk fields generates SM fermion masses with exponentially small bulk mass dependences. The SM fermion masses except for the top quark are shown to be reproduced by mild tuning of the bulk masses. The one-loop Higgs potential is calculated and it is shown that electroweak symmetry breaking occurs by introducing additional bulk fields. The Higgs boson mass is also computed.
Finite-N corrections to the superconformal index of S-fold theories
Authors: Arai Reona , Imamura Yosuke
Published: August 2019

We study the superconformal index of S-fold theories by using the anti-de Sitter / conformal field theory correspondence. It is known that the index in the large-$N$ limit is reproduced as the contribution of bulk Kaluza–Klein modes. For finite-$N$, D3-branes wrapped around the non-trivial cycle in $\boldsymbol{S}^5/\mathbb{Z}_k$, which corresponds to Pfaffian-like operators, give the corrections of order $q^N$ to the index. We calculate the finite-$N$ corrections by analyzing the fluctuations of wrapped D3-branes. Comparisons to known results show that our formula correctly reproduces the corrections up to errors of order $q^{2N}$.
Analytic construction of multi-brane solutions in cubic string field theory for any brane number
Authors: Hata Hiroyuki
Published: August 2019

We present an analytic construction of multi-brane solutions with any integer brane number in cubic open string field theory (CSFT) on the basis of the ${K\!Bc}$ algebra. Our solution is given in the pure-gauge form $\Psi=U{Q_\textrm{B}} U^{-1}$ by a unitary string field $U$, which we choose to satisfy two requirements. First, the energy density of the solution should reproduce that of the $(N+1)$-branes. Second, the equations of motion (EOM) of the solution should hold against the solution itself. In spite of the pure-gauge form of $\Psi$, these two conditions are non-trivial ones due to the singularity at $K=0$. For the $(N+1)$-brane solution, our $U$ is specified by $[N/2]$ independent real parameters $\alpha_k$. For the 2-brane ($N=1$), the solution is unique and reproduces the known one. We find that $\alpha_k$ satisfying the two conditions indeed exist as far as we have tested for various integer values of $N\ (=2, 3, 4, 5, \ldots)$. Our multi-brane solutions consisting only of the elements of the ${K\!Bc}$ algebra have the problem that the EOM is not satisfied against the Fock states and therefore are not complete ones. However, our construction should be an important step toward understanding the topological nature of CSFT, which has similarities to the Chern–Simons theory in three dimensions.
Industrial Policies in Production Networks*
Authors: Liu Ernest
Published: August 2019

Many developing economies adopt industrial policies favoring selected sectors. Is there an economic logic to this type of intervention? I analyze industrial policy when economic sectors form a production network via input-output linkages. Market imperfections generate distortionary effects that compound through backward demand linkages, causing upstream sectors to become the sink for imperfections and have the greatest size distortions. My key finding is that the distortion in sectoral size is a sufficient statistic for the social value of promoting that sector; thus, there is an incentive for a well-meaning government to subsidize upstream sectors. Furthermore, sectoral interventions’ aggregate effects can be simply summarized, to first order, by the cross-sector covariance between my sufficient statistic and subsidy spending. My sufficient statistic predicts sectoral policies in South Korea in the 1970s and modern-day China, suggesting that sectoral interventions might have generated positive aggregate effects in these economies.
Aggregation, Capital Heterogeneity, and the Investment CAPM
Authors: Gonçalves Andrei S , Xue Chen , Zhang Lu
Published: August 2019

A detailed treatment of aggregation and capital heterogeneity substantially improves the performance of the investment CAPM. Firm-level predicted returns are constructed from firm-level accounting variables and aggregated to the portfolio level to match with portfolio-level stock returns. Working capital forms a separate productive input besides physical capital. The model simultaneously fits the value, momentum, investment, and profitability premiums and partially explains positive stock-fundamental return correlations, the procyclical and short-term dynamics of the momentum and profitability premiums, and the countercyclical and long-term dynamics of the value and investment premiums. However, the model falls short in explaining momentum crashes.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online..
Sleep duration and quality are not associated with brown adipose tissue volume or activity—as determined by 18F-FDG uptake, in young, sedentary adults
Authors: Acosta Francisco M , Sanchez-Delgado Guillermo , Martinez-Tellez Borja , Migueles Jairo H , Amaro-Gahete Francisco J , Rensen Patrick C N , Llamas-Elvira Jose M , Blondin Denis P , Ruiz Jonatan R
Published: August 2019

Study Objectives

Short sleep duration and sleep disturbances have been related to obesity and metabolic disruption. However, the behavioral and physiological mechanisms linking sleep and alterations in energy balance and metabolism are incompletely understood. In rodents, sleep regulation is closely related to appropriate brown adipose tissue (BAT) thermogenic activity, but whether the same is true in humans has remained unknown. The present work examines whether sleep duration and quality are related to BAT volume and activity (measured by 18F-FDG) and BAT radiodensity in humans.

Methods

A total of 118 healthy adults (69% women, 21.9 ± 2.2 years, body mass index: 24.9 ± 4.7 kg/m2) participated in this cross-sectional study. Sleep duration and other sleep variables were measured using a wrist-worn accelerometer for seven consecutive days for 24 hours per day. The Pittsburgh Sleep Quality Index was used to assess sleep quality. All participants then underwent a personalized cold exposure to determine their BAT volume, activity, and radiodensity (a proxy of the intracellular triglyceride content), using static positron emission tomography combined with computed tomography (PET/CI) scan.

Results

Neither sleep duration nor quality was associated with BAT volume or activity (the latter represented by the mean and peak standardized 18F-FDG uptake values) or radiodensity (all p > .1). The lack of association remained after adjusting the analyses for sex, date of PET/CT, and body composition.

Conclusions

Although experiments in rodent models indicate a strong relationship to exist between sleep regulation and BAT function, it seems that sleep duration and quality may not be directly related to the BAT variables examined in the present work.

Clinical Trial Registration

NCT02365129 (ClinicalTrials.gov).
Maternal and congenital infections arising from Zika, dengue and Chikungunya arboviruses in Salvador, Brazil
Authors: Duarte Alan Oliveira , Oliveira João Vitor , Carvalho Tereza Cristina Xavier , Pessoa Lorena de Brito , Filho Cláudio Magalhães , Lima Jéssica Graziele Souza , Carvalho Daniel Augusto , dos Santos Daiana Carlos , Santos Cleiton Silva , Pessoa Rosana , Souza Gloryane Bessa , Calcagno Juan Ignacio , Santana Edilene Mota , de Oliveira Aline Sousa , Francisco Marcos Vinicius Lima de Oliveira , Costa Bernardo Gratival Gouvea , Gomes Lillian Nunes , Romero Fernando , Khouri Ricardo , Alcântara Luiz Carlos , Lima Fernanda Washington de Mendonça , de Siqueira Isadora Cristina
Published: August 2019

Background

Salvador was one of the Brazilian cities most affected during the 2015 Zika virus (ZIKV) outbreak.

Methods

A cross-sectional study was performed with enrolment of parturients and their newborns.

Results

Positive IgM antibodies for ZIKV, dengue (DENV) and Chikungunya (CHIKV) were present in 6.9, 11.9 and 22.8% of the parturients, and IgG antibodies were detected in 72.3, 92.3 and 38.6%, respectively. No cases of DENV congenital infection were identified. ZIKV and CHIKV congenital infections were observed in 16.5 and 13% of newborns, respectively.

Conclusions

High exposure rates to the three arboviruses and the identification of newborns with ZIKV and CHIKV congenital infections reinforces the necessity of ZIKV and CHIKV prenatal and neonatal screening in endemic regions.
Phylogeny and biogeography of the Brazilian–Guiana Shield endemic Corymbophanes clade of armoured catfishes (Loricariidae)
Authors: Lujan Nathan K , Armbruster Jonathan W , Werneke David C , Teixeira Túlio Franco , Lovejoy Nathan R
Published: August 2019

Numerous rivers, interrupted by large waterfalls and extensive rapids, drain the geologically ancient Guiana Shield Highlands. We describe a new armoured catfish genus and two new species endemic to the upper Ireng and Kuribrong rivers, respective tributaries of the Amazon and Essequibo basins in western Guiana. Corymbophanes ameliae sp. nov. is distinguished by having vermiculations on the abdomen, bands on the caudal fin, the anal fin i,5 and narrow caudal peduncle. Yaluwak primus gen. & sp. nov. is distinguished by having evertible cheek odontodes, a plated snout, a tall caudal peduncle and absence of adipose fin and iris operculum. We present a new molecular phylogenetic analysis inclusive of these and several related genera that suggests that the Corymbophanes clade (Araichthys, Corymbophanes, Cryptancistrus, Guianancistrus, Hopliancistrus and Yaluwak) originated in the Guiana Shield with secondary dispersal to the Brazilian Shield. Within the Guiana Shield, relationships among Corymbophanes and Yaluwak are consistent with geodispersal between drainages via headwater capture, although an uplift-mediated relictual distribution cannot be ruled out. ND2 haplotype structure among C. ameliae populations suggests that ichthyofaunal diversity on the Guiana Shield escarpment is shaped not only by inter-, but also intrafluvial barriers to gene flow.
Controlled induction and targeted elimination of p16INK4a‐expressing chondrocytes in cartilage explant culture
Authors: Sessions Garrett A. , Copp Michaela E. , Liu Jie‐Yu , Sinkler Margaret A. , D'Costa Susan , Diekman Brian O.
Published: August 2019

Cellular senescence is a phenotypic state that contributes to age‐related diseases through the secretion of matrix‐degrading and inflammatory molecules. An emerging therapeutic strategy for osteoarthritis (OA) is to selectively eliminate senescent cells by initiating apoptosis. This study establishes a cartilage explant model of senescence induction and senolytic clearance using p16Ink4a expression as a biomarker of senescence. Growth‐factor stimulation of explants increased the expression of p16Ink4a at both the mRNA and protein levels. Applying this culture system to cartilage from p16tdTom reporter mice (a knockin allele with tdTomato fluorescent protein regulated by the endogenous p16Ink4a promoter) demonstrated the emergence of a p16‐high population that was quantified using flow cytometry for tdTomato. Cell sorting was used to separate chondrocytes based on tdTomato fluorescence and p16‐high cells showed higher senescence‐associated β‐galactosidase activity and increased gene expression of the senescence‐associated secretory phenotype as compared with p16‐low cells. The potential for effective senolysis within the cartilage extracellular matrix was assessed using navitoclax (ABT‐263). Navitoclax treatment reduced the percentage of p16‐high cells from 17.9 to 6.1% (mean of 13 matched pairs; P < 0.001) and increased cleaved caspase‐3 confirmed apoptotic activity. Together, these findings establish a physiologically relevant cartilage explant model for testing the induction and elimination of senescent chondrocytes, which will support investigations of senolytic therapy for OA.—Sessions, G. A., Copp, M. E., Liu, J.‐Y., Sinkler, M. A., D'Costa, S., Diekman, B. O. Controlled induction and targeted elimination of p16INK4a‐expressing chondrocytes in cartilage explant culture. FASEB J. 33, 12364–12373 (2019). www.fasebj.org
Hypergammaglobulinemia and Impaired Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea
Authors: Atwell Jessica E. , Thumar Bhagvanji , Formica Maria A. , Robinson Leanne J. , Walsh Edward E. , King Christopher L. , Karron Ruth A.
Published: August 2019

Background:

Passively-acquired respiratory syncytial virus (RSV) neutralizing antibody (Ab) can protect against RSV-associated lower respiratory tract illness. Maternal RSV immunization is, therefore, an attractive strategy for protection of very young infants. Vaccines for this purpose are currently being evaluated in clinical trials, but conditions such as preterm birth, placental malaria, maternal hypergammaglobulinemia and HIV infection might threaten this strategy. Each has been shown to impair transplacental Ab transfer for a variety of pathogens, but RSV-specific data are limited. Work in The Gambia demonstrated that placental malaria impaired transplacental transfer of RSV Ab, but a subsequent study in malaria-endemic Papua New Guinea (PNG) indicated that such associations may have been confounded by hypergammaglobulinemia (IgG > 1700 mg/dL).

Methods:

Here we confirm and extend those findings by measuring RSV neutralizing Ab and maternal IgG in sera from a larger cohort of 325 mother/infant pairs in PNG, and demonstrate the applicability of a high-throughput assay for assessment of neutralizing Ab.

Results:

One-third of mother-infant pairs demonstrated impaired RSV Ab transfer. Infants of hypergammaglobulinemic women were more likely to have both impaired transfer [cord-to-maternal titer ratio <1.0, adjusted odds ratio (OR): 3.36 (95% confidence interval: 1.81–6.30)] and the lowest RSV cord titers [adjusted OR: 5.09 (95% confidence interval: 1.95–13.32, P < 0.001)], but neither outcome was associated with placental malaria.

Conclusions:

Once maternal RSV vaccines become available, successful implementation will require clear understanding and mitigation of factors that can impair passive protection, necessitating epidemiologic studies of such relationships ahead of vaccine availability. This study underscores the need to focus on hypergammaglobulinemia as a condition of importance.
Long-term Vaccine Impact on Invasive Pneumococcal Disease Among Children With Significant Comorbidities in a Large Australian Birth Cohort
Authors: Jayasinghe Sanjay , Liu Bette , Gidding Heather , Gibson Amy , Chiu Clayton , McIntyre Peter
Published: August 2019

Background:

Little is known about long-term invasive pneumococcal disease (IPD) incidence in children with risk factors (RFs) in populations with high coverage pneumococcal conjugate vaccine (PCV) programs. We measured IPD burden and changes with PCV use in children by RF status.

Methods:

A retrospective cohort of all live births in 2001–2012 in New South Wales, Australia was linked to IPD, hospitalization and death data. RFs were identified from International Classification of Diseases codes in linked hospitalizations. For each RF adjusted hazard ratios (aHRs, using Cox models), population attributable fractions (PAFs) and changes post-PCV relative to baseline for IPD were calculated.

Results:

One-thousand two-hundred fifty-one IPD cases occurred in ~1.1 million children in 12-year study cohort. The 75,404 children (6.8% of cohort) with RFs accounted for 255 (20.4%) IPD cases [rate (per 100,000 person-years) of 61 compared with 14 in no RFs]. Asthma was most common RF (n = 41,074; 3.6%) but highest IPD risk was in 2452 children (0.2%) with immunosuppression, splenic dysfunction or breach in cerebrospinal fluid barrier (aHR~20; PAF 0.7–1.8%) versus asthma (aHR 5.3; PAF 14.8%). Compared with 2001–2004 birth cohort (baseline), IPD incidence in PCV-eligible 2009–2012 birth cohort was 78% (95% confidence interval: –72% to –82%) less in children without RFs. IPD declined nonsignificantly (13%; 95% confidence interval: –70% to +138%) in highest IPD risk group, but by 67% (–43% to –82%) in children with other RFs.

Conclusions:

By 8 years of universal PCV, IPD incidence reduced significantly in all children except in the 0.2% at highest risk, for whom antibiotic prophylaxis and additional vaccine doses are recommended but compliance and effectiveness remain uncertain.
Whole-brain functional network disruption in chronic pain with disk herniation
Authors: Huang Shishi , Wakaizumi Kenta , Wu Binbin , Shen Bangli , Wu Bo , Fan Linyu , Baliki Marwan N. , Zhan Gonghao , Apkarian A. Vania , Huang Lejian
Published: August 2019

Brain functional network properties are globally disrupted in multiple musculoskeletal chronic pain conditions. Back pain with lumbar disk herniation (LDH) is highly prevalent and a major route for progression to chronic back pain. However, brain functional network properties remain unknown in such patients. Here, we examined resting-state functional magnetic resonance imaging-based functional connectivity networks in chronic back pain patients with clear evidence for LDH (LDH-chronic pain n = 146), in comparison to healthy controls (HCs, n = 165). The study was conducted in China, thus providing the opportunity to also examine the influence of culture on brain functional reorganization with chronic pain. The data were equally subdivided into discovery and validation subgroups (n = 68 LDH-chronic pain and n = 68 HC, for each subgroup), and contrasted to an off-site data set (n = 272, NITRC 1000). Graph disruption indices derived from 3 network topological measurements, degree, clustering coefficient, and efficiency, which respectively represent network hubness, segregation, and integration, were significantly decreased compared with HC, across all predefined link densities, in both discovery and validation groups. However, global mean clustering coefficient and betweenness centrality were decreased in the discovery group and showed trend in the validation group. The relationship between pain and graph disruption indices was limited to males with high education. These results deviate somewhat from recent similar analysis for other musculoskeletal chronic pain conditions, yet we cannot determine whether the differences are due to types of pain or also to cultural differences between patients studied in China and the United States.
Heme and sensory neuropathy: insights from novel mutations in the heme exporter feline leukemia virus subgroup C receptor 1
Authors: Bertino Francesca , Firestone Kyra , Bellacchio Emanuele , Jackson Kelly E. , Asamoah Alexander , Hersh Joseph , Fiorito Veronica , Destefanis Francesca , Gonser Rusty , Tucker Megan E. , Altruda Fiorella , Tolosano Emanuela , Chiabrando Deborah
Published: August 2019

Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system mainly characterized by impaired nociception and autonomic dysfunction. We previously identified heme metabolism as a novel pathway contributing to sensory neurons maintenance and nociception. Indeed, we reported mutations in the feline leukemia virus subgroup C receptor 1 (FLVCR1) gene in individuals affected by HSAN. FLVCR1 gene encodes for 2 heme export proteins, FLVCR1a (plasma membrane) and FLVCR1b (mitochondria), crucially involved in the regulation of cellular heme homeostasis. Here, we report on 2 additional patients carrying novel biallelic mutations in FLVCR1 translation initiation codon (c.2T>C; p.(Met1Thr) and c.3G>T; p.(Met1Ile)). We overexpressed the c.2T>C; p.(Met1Thr) mutant in human cell lines and we describe its impact on protein structure and function in comparison with other HSAN-related mutations. We found that the mutation interferes with translation in 2 different ways: by lowering levels of translation of wild-type protein and by inducing translation initiation from a downstream in-frame ATG, leading to the production of an N-terminal truncated protein that is retained in the endoplasmic reticulum. The impact of different kinds of mutations on FLVCR1a localization and structure was also described. The identification of novel FLVCR1 mutations in HSAN reinforces the crucial role of heme in sensory neuron maintenance and pain perception. Moreover, our in vitro findings demonstrate that heme export is not completely lost in HSAN patients, thus suggesting the possibility to improve FLVCR1 expression/activity for therapeutic purposes.
Clinical utility of genomic sequencing
Authors: Neu Matthew B. , Bowling Kevin M. , Cooper Gregory M.
Published: August 2019

Purpose of review

Identifying pathogenic variation underlying pediatric developmental disease is critical for medical management, therapeutic development, and family planning. This review summarizes current genetic testing options along with their potential benefits and limitations. We also describe results from large-scale genomic sequencing projects in pediatric and neonatal populations with a focus on clinical utility.

Recent findings

Recent advances in DNA sequencing technology have made genomic sequencing a feasible and effective testing option in a variety of clinical settings. These cutting-edge tests offer much promise to both medical providers and patients as it has been demonstrated to detect causal genetic variation in ∼25% or more of previously unresolved cases. Efforts aimed at promoting data sharing across clinical genetics laboratories and systematic reanalysis of existing genomic sequencing data have further improved diagnostic rates and reduced the number of unsolved cases.

Genomic sequencing is a powerful and increasingly cost-effective alternative to current genetic tests and will continue to grow in clinical utility as more of the genome is understood and as analytical methods are improved. The evolution of genomic sequencing is changing the landscape of clinical testing and requires medical professionals who are adept at understanding and returning genomic results to patients.
Outcomes measures in children after acute central nervous system infections and malaria
Authors: Postels Douglas G. , Soldatos Ariane , LaRovere Kerri L.
Published: August 2019

Purpose of review

Acute central nervous system (CNS) infections in children result in significant mortality and neurologic morbidity worldwide. This article summarizes the recent pediatric literature published on outcomes measures used after acute infectious meningitis, encephalitis, and cerebral malaria, and highlights ongoing research efforts to standardize outcomes measurements. Search terms were geared toward functional, cognitive, behavioral, and other outcome assessments.

Recent findings

Recent data suggest that, depending on microbiological cause, there are differences in currently used outcome measures following acute CNS infections. Outcomes assessments include a variety of formal psychological tests (structured interviews and neuropsychological tests of cognitive and motor functioning) and dichotomized or ordinal scales. Standardization of outcome measures, however, is lacking. Global efforts to standardize outcomes that encompass both the child and family are ongoing.

Centers worldwide can track and measure a variety of cognitive, behavioral, and functional outcomes after acute CNS infections. Standardized documentation and coding of clinically important outcomes is needed. Further research to evaluate effective practices using acute adjunctive and rehabilitation therapies will be aided by outcome measure standardization.
Advances in primary mitochondrial myopathies
Authors: de Barcelos Isabella Peixoto , Emmanuele Valentina , Hirano Michio
Published: August 2019

Purpose of review

Although mitochondrial diseases impose a significant functional limitation in the lives of patients, treatment of these conditions has been limited to dietary supplements, exercise, and physical therapy. In the past few years, however, translational medicine has identified potential therapies for these patients.

Recent findings

For patients with primary mitochondrial myopathies, preliminary phase I and II multicenter clinical trials of elamipretide indicate safety and suggest improvement in 6-min walk test (6MWT) performance and fatigue scales. In addition, for thymidine kinase 2-deficient (TK2d) myopathy, compassionate-use oral administration of pyrimidine deoxynucleosides have shown preliminary evidence of safety and efficacy in survival of early onset patients and motor functions relative to historical TK2d controls.

The prospects of effective therapies that improve the quality of life for patients with mitochondrial myopathy underscore the necessity for definitive diagnoses natural history studies for better understanding of the diseases.
Prevalence of diabetic foot ulcer and its association with duration of illness and residence in Ethiopia: a systematic review and meta-analysis
Authors: Mulugeta Henok , Wagnew Fasil , Zeleke Haymanot , Tesfaye Bekele , Amha Haile , Leshargie Cheru Tesema , Biresaw Henok , Dessie Getenet , Belay Yihalem Abebe , Habtewold Tesfa Dejenie
Published: August 2019

Background

Diabetic foot ulcer (DFU), devastating complications of diabetes mellitus, is a major public health problem, and one of the leading reasons for hospital admission, amputations, and even death among diabetic patients in Ethiopia. Despite its catastrophic health consequences, the national burden of diabetic foot ulcer remains unknown in Ethiopia. Hence, the objective of this systematic review and meta-analysis was to estimate the national prevalence of diabetic foot ulcer and investigate the association with duration of illness and patient residence among diabetic patients.

Methods

We searched PubMed, Google Scholar, Cochrane Library, CINAHL, EMBASE, and PsycINFO databases for studies of diabetic foot ulcers prevalence that published from conception up to June 30, 2019. Quality of each article was assessed using a modified version of the Newcastle-Ottawa Scale for cross-sectional studies. All statistical analyses were done using STATA version 14 software for Windows, and meta-analysis was carried out using a random-effects method. The pooled national prevalence of diabetic foot ulcers was presented using a forest plot.

Results

A total of 10 studies with 3,029 diabetic patients were included. The pooled national prevalence of diabetic foot ulcers among Ethiopian diabetic patients was 11.27% (95% CI 7.22, 15.31%, I2=94.6). Duration of illness (OR: 3.91, 95%CI 2.03, 7.52, I2=63.4%) and patients’ residence (OR: 3.40, 95%CI 2.09, 5.54, I2=0.0%) were significantly associated with a diabetic foot ulcer.

Conclusion

In Ethiopia, at least one out of ten diabetic patients had diabetic foot ulcers. Healthcare policymakers (FMoH) need to improve the standard of diabetic care and should design effective preventive strategies to improve health care delivery for people with diabetes and reduce the risk of foot ulceration.
Impact of pediatric influenza vaccination on antibiotic resistance in England and Wales
Authors: Chae Chungman , Davies Nicholas G. , Jit Mark , Atkins Katherine E.
Published: August 2019

Vaccines against viral infections have been proposed to reduce antibiotic prescribing and thereby help control resistant bacterial infections. However, by combining published data sources, we predict that pediatric live attenuated influenza vaccination in England and Wales will not have a major impact upon antibiotic consumption or health burdens of resistance.
A flexible formula for incorporating distributive concerns into cost-effectiveness analyses: priority weights
Authors: Haaland Ø.A. , Lindemark F. , Johansson K.A.
Published: August 2019

Cost effectiveness analyses (CEAs) are widely used to evaluate the opportunity cost of health care investments. However, few functions that take equity concerns into account are available for such CEA methods, and these concerns are therefore at risk of being disregarded. Among the functions that have been developed, most focus on the distribution of health gains, as opposed to the distribution of lifetime health. This is despite the fact that there are good reasons to give higher priority to individuals and groups with a low health adjusted life expectancy. Also, an even distribution of health gains may imply an uneven distribution of lifetime health.

We develop a systematic and explicit approach that allows for the inclusion of lifetime health concerns in CEAs, by creating a new priority weight function, PW=α+(t-γ)·C·e-β·(t-γ), where t is the health measure. PW has several desirable properties. First, it is continuous and smooth, ensuring that people with similar health characteristics are treated alike. Second, it is flexible regarding shape and outcome measure, so that a broad range of values may be modelled.

Third, the coefficients have distinct roles. This allows for the easy manipulation of the PW’s shape. In order to demonstrate how PW may be applied, we use data from a previous study and estimated the coefficients of PW based on two approaches.

The first considers the mean weights assigned by the respondents:

PWmean=-0.42+(t+22.2)·0.27·e-0.031·(t+22.2).

The second considers the median weights:

PWmedian=0.79+(t+8.85)·0.17·e-0.053·(t+8.85).

This illustrates that our framework allows for the estimation of PWs based on empirical data.
PathFlowAI: A High-Throughput Workflow for Preprocessing, Deep Learning and Interpretation in Digital Pathology
Authors: Levy Joshua J. , Salas Lucas A. , Christensen Brock C. , Sriharan Aravindhan , Vaickus Louis J.
Published: August 2019

The diagnosis of disease often requires analysis of a biopsy. Many diagnoses depend not only on the presence of certain features but on their location within the tissue. Recently, a number of deep learning diagnostic aids have been developed to classify digitized biopsy slides. Clinical workflows often involve processing of more than 500 slides per day. But, clinical use of deep learning diagnostic aids would require a preprocessing workflow that is cost-effective, flexible, scalable, rapid, interpretable, and transparent. Here, we present such a workflow, optimized using Dask and mixed precision training via APEX, capable of handling any patch-level or slide level classification and prediction problem. The workflow uses a flexible and fast preprocessing and deep learning analytics pipeline, incorporates model interpretation and has a highly storage-efficient audit trail. We demonstrate the utility of this package on the analysis of a prototypical anatomic pathology specimen, liver biopsies for evaluation of hepatitis from a prospective cohort. The preliminary data indicate that PathFlowAI may become a cost-effective and time-efficient tool for clinical use of Artificial Intelligence (AI) algorithms.