bluuebunny/crossref_metadata_2025 huggingface dataset:
Propane clusters in Titan’s lower atmosphere: insights from a combined theory/laboratory study
Authors: Bourgalais J , Durif O , Le Picard S D , Lavvas P , Calvo F , Klippenstein S J , Biennier L
Published: June 2019

In spite of the considerable advances made by Cassini–Huygens in our understanding of Titan, many questions endure. In particular, the detailed processes that lead to the formation of haze aerosols in Titan’s atmosphere, found in high concentrations at low altitudes, are not well identified. Hydrocarbons, which are abundant constituents of Titan’s cold atmosphere originating from photochemical processes, may simultaneously condense on the surface of existing aerosols, nucleate and grow to generate new aerosol seeds. The relative importance of the various processes depends on several factors, including the saturation ratio. The dynamics of hydrocarbon condensation and nucleation in Titan’s atmosphere remains poorly known. Aiming to progress on these issues, we investigate here the kinetics of propane dimer formation at low temperature through state-of-the-art laboratory experiments combined with theoretical calculations. Our results provide an estimate of the rate coefficients, which are then employed to evaluate the abundance of propane dimers in the lower atmosphere of Titan. The mixing ratios of propane dimers inferred, with a maximum abundance of 10 cm−3 near 100 km, is found to be under the detection limit of the Composite Infrared Spectrometer of the Cassini spacecraft. Based on our results, homogeneous nucleation of the most abundant species appears not to be relevant for the growth of aerosols. Future studies should focus on homogeneous nucleation of polar molecules or alternatively on heterogeneous processes, which are usually more efficient.
Energy occupation of waves and structures in 3D compressive MHD turbulence
Authors: Yang L P , Li H , Li S T , Zhang L , He J S , Feng X S
Published: June 2019

Structures and propagating waves are often observed in solar wind turbulence. Their origins and features remain to be uncovered. In this work, we use 3D driven, compressible MHD turbulence simulations to investigate the global signatures of the driven fluctuations in whole spatial and temporal domain. With four-dimensional spatial-temporal (x, y, z, t) Fourier transformations implemented, we have identified two distinct main populations: waves, which satisfy the $\omega -\boldsymbol {k}$ dispersion relations and are propagating; and structures, which satisfy the polarization relations but non-propagating (ω = 0). Whereas the overall turbulent energy spectrum is still consistent with k−5/3, the contributions from waves and structures show very different behaviour in $\boldsymbol {k}$ space, with structures dominating at small k but waves becomes comparable to structures at large k. Overall, the fluctuations in the directions perpendicular to the large-scale mean field $\boldsymbol {B_0}$ are a manifestation of structures, while along the parallel direction, the fluctuations are dominated by waves. Also, a significant portion of the incompressible structures are the Alfvénic nature, and with imbalanced increased, the waves predominantly propagate in one direction and nearly perpendicular to $\boldsymbol {B_0}$. Differentiating the relative contributions from waves and structures could have important implications for understanding the non-linear cascade processes in the inertial range as well as particle-fluctuation interactions at small scales.
The use of convolutional neural networks for modelling large optically-selected strong galaxy-lens samples
Authors: Pearson James , Li Nan , Dye Simon
Published: June 2019

We explore the effectiveness of deep learning convolutional neural networks (CNNs) for estimating strong gravitational lens mass model parameters. We have investigated a number of practicalities faced when modelling real image data, such as how network performance depends on the inclusion of lens galaxy light, the addition of colour information, and varying signal-to-noise. Our CNN was trained and tested with strong galaxy–galaxy lens images simulated to match the imaging characteristics of the Large Synoptic Survey Telescope (LSST) and Euclid. For images including lens galaxy light, the CNN can recover the lens model parameters with an acceptable accuracy, although a 34 per cent average improvement in accuracy is obtained when lens light is removed. However, the inclusion of colour information can largely compensate for the drop in accuracy resulting from the presence of lens light. While our findings show similar accuracies for single epoch Euclid VIS and LSST r-band data sets, we find a 24 per cent increase in accuracy by adding g- and i-band images to the LSST r-band without lens light and a 20 per cent increase with lens light. The best network performance is obtained when it is trained and tested on images where lens light exactly follows the mass, but when orientation and ellipticity of the light are allowed to differ from those of the mass, the network performs most consistently when trained with a moderate amount of scatter in the difference between the mass and light profiles.
On the nature of variations in the measured star formation efficiency of molecular clouds
Authors: Grudić Michael Y , Hopkins Philip F , Lee Eve J , Murray Norman , Faucher-Giguère Claude-André , Johnson L Clifton
Published: June 2019

Measurements of the star formation efficiency (SFE) of giant molecular clouds (GMCs) in the Milky Way generally show a large scatter, which could be intrinsic or observational. We use magnetohydrodynamic simulations of GMCs (including feedback) to forward-model the relationship between the true GMC SFE and observational proxies. We show that individual GMCs trace broad ranges of observed SFE throughout collapse, star formation, and disruption. Low measured SFEs (${\ll} 1\hbox{ per cent}$) are ‘real’ but correspond to early stages; the true ‘per-freefall’ SFE where most stars actually form can be much larger. Very high (${\gg} 10\hbox{ per cent}$) values are often artificially enhanced by rapid gas dispersal. Simulations including stellar feedback reproduce observed GMC-scale SFEs, but simulations without feedback produce 20× larger SFEs. Radiative feedback dominates among mechanisms simulated. An anticorrelation of SFE with cloud mass is shown to be an observational artefact. We also explore individual dense ‘clumps’ within GMCs and show that (with feedback) their bulk properties agree well with observations. Predicted SFEs within the dense clumps are ∼2× larger than observed, possibly indicating physics other than feedback from massive (main-sequence) stars is needed to regulate their collapse.
Advances and Applications in the Quest for Orthologs
Authors: Glover Natasha , Dessimoz Christophe , Ebersberger Ingo , Forslund Sofia K , Gabaldón Toni , Huerta-Cepas Jaime , Martin Maria-Jesus , Muffato Matthieu , Patricio Mateus , Pereira Cécile , da Silva Alan Sousa , Wang Yan , Sonnhammer Erik , Thomas Paul D
Published: June 2019

Gene families evolve by the processes of speciation (creating orthologs), gene duplication (paralogs), and horizontal gene transfer (xenologs), in addition to sequence divergence and gene loss. Orthologs in particular play an essential role in comparative genomics and phylogenomic analyses. With the continued sequencing of organisms across the tree of life, the data are available to reconstruct the unique evolutionary histories of tens of thousands of gene families. Accurate reconstruction of these histories, however, is a challenging computational problem, and the focus of the Quest for Orthologs Consortium. We review the recent advances and outstanding challenges in this field, as revealed at a symposium and meeting held at the University of Southern California in 2017. Key advances have been made both at the level of orthology algorithm development and with respect to coordination across the community of algorithm developers and orthology end-users. Applications spanned a broad range, including gene function prediction, phylostratigraphy, genome evolution, and phylogenomics. The meetings highlighted the increasing use of meta-analyses integrating results from multiple different algorithms, and discussed ongoing challenges in orthology inference as well as the next steps toward improvement and integration of orthology resources.
Achieving tight control of a photoactivatable Cre recombinase gene switch: new design strategies and functional characterization in mammalian cells and rodent
Authors: Meador Kyle , Wysoczynski Christina L , Norris Aaron J , Aoto Jason , Bruchas Michael R , Tucker Chandra L
Published: June 2019

A common mechanism for inducibly controlling protein function relies on reconstitution of split protein fragments using chemical or light-induced dimerization domains. A protein is split into fragments that are inactive on their own, but can be reconstituted after dimerization. As many split proteins retain affinity for their complementary half, maintaining low activity in the absence of an inducer remains a challenge. Here, we systematically explore methods to achieve tight regulation of inducible proteins that are effective despite variation in protein expression level. We characterize a previously developed split Cre recombinase (PA-Cre2.0) that is reconstituted upon light-induced CRY2-CIB1 dimerization, in cultured cells and in vivo in rodent brain. In culture, PA-Cre2.0 shows low background and high induced activity over a wide range of expression levels, while in vivo the system also shows low background and sensitive response to brief light inputs. The consistent activity stems from fragment compartmentalization that shifts localization toward the cytosol. Extending this work, we exploit nuclear compartmentalization to generate light-and-chemical regulated versions of Cre recombinase. This work demonstrates in vivo functionality of PA-Cre2.0, describes new approaches to achieve tight inducible control of Cre DNA recombinase, and provides general guidelines for further engineering and application of split protein fragments.
Insights into the G-rich VEGF-binding aptamer V7t1: when two G-quadruplexes are better than one!
Authors: Moccia Federica , Riccardi Claudia , Musumeci Domenica , Leone Serena , Oliva Rosario , Petraccone Luigi , Montesarchio Daniela
Published: June 2019

The G-quadruplex-forming VEGF-binding aptamer V7t1 was previously found to be highly polymorphic in a K+-containing solution and, to restrict its conformational preferences to a unique, well-defined form, modified nucleotides (LNA and/or UNA) were inserted in its sequence. We here report an in-depth biophysical characterization of V7t1 in a Na+-rich medium, mimicking the extracellular environment in which VEGF targeting should occur, carried out combining several techniques to analyse the conformational behaviour of the aptamer and its binding to the protein. Our results demonstrate that, in the presence of high Na+ concentrations, V7t1 behaves in a very different way if subjected or not to annealing procedures, as evidenced by native gel electrophoresis, size exclusion chromatography and dynamic light scattering analysis. Indeed, not-annealed V7t1 forms both monomeric and dimeric G-quadruplexes, while the annealed oligonucleotide is a monomeric species. Remarkably, only the dimeric aptamer efficiently binds VEGF, showing higher affinity for the protein compared to the monomeric species. These findings provide new precious information for the development of improved V7t1 analogues, allowing more efficient binding to the cancer-related protein and the design of effective biosensors or theranostic devices based on VEGF targeting.
The Inference to the Best Legal Explanation
Authors: Michelon Claudio
Published: June 2019

Courts use inferences to the best explanation in many contexts and for a variety of purposes. Yet our understanding of lawyers’ uses of this inferential form is insufficient. In this article, after briefly introducing this inferential form, I set out to: (i) explain the structure of such arguments by reference to an argument scheme; (ii) clarify the types of claims courts support by deploying such inferences while attempting to justify acting in accordance with explanatory principles (inferences to the best explanation—principles, or IBE-Ps); (iii) offer an account of the ‘explanatory’ relationship on which IBE-P is predicated; (iv) explain what precisely can count as part of the explanandum in an IBE-P; and (v) discuss criteria that might be used to adjudicate which is the best among rival explanations.
Is the ‘Mere Equity’ to Rescind a Legal Power? Unpacking Hohfeld’s Concept of ‘Volitional Control’
Authors: Reilly Adam
Published: June 2019

Private lawyers owe a particular debt of gratitude to Hohfeld, given their widespread use of his scheme. An example is equitable rescission, where the entitlement to rescind a voidable transfer is now widely understood to be a Hohfeldian legal power. Yet, though scholars have been quick to use Hohfeld’s concept of legal power, they have given little sustained thought to what he meant by ‘volitional control’ and how we might identify it within the law. The result is that certain areas of law have been mislabelled as ‘power conferring’, most notably equitable rescission. This article seeks to unpack Hohfeld’s concept of ‘volitional control’ as terminological shorthand for the coincidence of two distinct elements: (i) the power holder’s normative intention to effect the relevant legal change; and (ii) her decision to effect that change as exhibited in power-exercising conduct. By these lights, the rescinding claimant does not have a legal power to rescind.
Structure-Specific Regulation of Nutrient Transport and Metabolism in Arbuscular Mycorrhizal Fungi
Authors: Kameoka Hiromu , Maeda Taro , Okuma Nao , Kawaguchi Masayoshi
Published: June 2019

Arbuscular mycorrhizal fungi (AMF) establish symbiotic relationships with most land plants, mainly for the purpose of nutrient exchange. Many studies have revealed the regulation of processes in AMF, such as nutrient absorption from soil, metabolism and exchange with host plants, and the genes involved. However, the spatial regulation of the genes within the structures comprising each developmental stage is not well understood. Here, we demonstrate the structure-specific transcriptome of the model AMF species, Rhizophagus irregularis. We performed an ultra-low input RNA-seq analysis, SMART-seq2, comparing five extraradical structures, germ tubes, runner hyphae, branched absorbing structures (BAS), immature spores and mature spores. In addition, we reanalyzed the recently reported RNA-seq data comparing intraradical mycelium and arbuscule. Our analyses captured the distinct features of each structure and revealed the structure-specific expression patterns of genes related to nutrient transport and metabolism. Of note, the transcriptional profiles suggest distinct functions of BAS in nutrient absorption. These findings provide a comprehensive dataset to advance our understanding of the transcriptional dynamics of fungal nutrition in this symbiotic system.
The Impact of Tax and Expenditure Limitations on User Fees and Charges in Local Government Finance: Evidence from New England
Authors: Zhang Pengju , Hou Yilin
Published: June 2019

American local government financing shifted from taxation toward user fees and charges (UFCs) in the late 1970s, with substantial efficiency and equity implications. Normatively, the shift aligns with the benefit principle; positively, the shift is often attributed to tax revolts. We test the two associations via a difference-in-differences design and a fiscal stringency measure of tax and expenditure limitations (TELs); we also test the moderating effects of overrides on TELs. Our results confirm that state-imposed TELs caused the shift in local public finance; the results are robust to change of sample and empirical strategy. This article helps explain the relationship between tax revolts and non-tax revenue and provides evidence that fiscal constraints imposed by a higher level government on a constituent level can have significant effects, including effects beyond the intent of the constraints’ framers.
Testing Beta-Pricing Models Using Large Cross-Sections
Authors: Raponi Valentina , Robotti Cesare , Zaffaroni Paolo
Published: June 2019

We propose a methodology for estimating and testing beta-pricing models when a large number of assets is available for investment but the number of time-series observations is fixed. We first consider the case of correctly specified models with constant risk premia, and then extend our framework to deal with time-varying risk premia, potentially misspecified models, firm characteristics, and unbalanced panels. We show that our large cross-sectional framework poses a serious challenge to common empirical findings regarding the validity of beta-pricing models. In the context of pricing models with Fama-French factors, firm characteristics are found to explain a much larger proportion of variation in estimated expected returns than betas.

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.
CONE BEAM CT IN DENTAL IMPLANT PLANNING: HOW CLOSE ARE PATIENT DOSIMETRY RESULTS WITH DATA FROM PHANTOM STUDIES FOUND IN LITERATURE?
Authors: Kottou S , Zapros A , Stefanopoulou N , Krompas N , Tsapaki V
Published: June 2019

Advantages of Cone Beam Computed Tomography (CBCT) include high-quality 3D imaging and reduced radiation exposure with relatively low cost. In this study, patient radiation exposure in CBCT implant planning dentistry was measured in terms of Kerma Area Product (KAP). Data were obtained from 217 CBCT scans on 168 individuals using a CS9300 Carestream system. Scans were made using 80–90 kVp, 4–5 mA, 8 and 13.3 s exposure time (depending on voxel size) and a fixed field of view (FOV) of 10 × 10 cm2 (medium). Mean KAP was estimated using two voxel sizes 180 × 180 × 180 μm3 and 200 × 200 × 200 μm3 and found to be 399 and 314 mGycm2, respectively. Corresponding KAP values found in literature ranged between 210 and 2140 mGycm2. Mean E was estimated using conversion coefficient factors found in literature, according to FOV size and tube voltage value and found to range between 24 and 161 μSv.
Single Session Transcranial Magnetic Stimulation Ameliorates Hand Gesture Deficits in Schizophrenia
Authors: Walther Sebastian , Kunz Maribel , Müller Manuela , Zürcher Caroline , Vladimirova Irena , Bachofner Hanta , Scherer Konstantin A , Nadesalingam Niluja , Stegmayer Katharina , Bohlhalter Stephan , Viher Petra V
Published: June 2019

Social interaction is impaired in schizophrenia, including the use of hand gestures, which is linked to poor social perception and outcome. Brain imaging suggests reduced neural activity in a left-lateralized frontoparietal network during gesture preparation; therefore, gesturing might be improved through facilitation of left hemispheric brain areas or via disruption of interhemispheric inhibition from the right homolog. This study tested whether repetitive transcranial magnetic stimulation (rTMS) protocols would improve gesture performance in schizophrenia. This randomized, placebo-controlled, double-blind, crossover trial applied 3 different protocols of rTMS separated by 48 h. Twenty right-handed schizophrenia patients and 20 matched healthy controls received facilitatory intermittent theta burst stimulation (iTBS) over the left inferior frontal gyrus (IFG), inhibitory continuous theta burst stimulation (cTBS) over right inferior parietal lobe (IPL), and placebo over left IPL in randomized order. Primary outcome was change in the test of upper limb apraxia (TULIA), rated from video recordings of hand gesture performance. Secondary outcome was change in manual dexterity using the coin rotation task. Participants improved on both tasks following rTMS compared with baseline. Only patients improved gesture performance following right IPL cTBS compared with placebo (P = .013). The results of the coin rotation parallel those of the TULIA, with improvements following right IPL cTBS in patients (P = .001). Single sessions of cTBS on the right IPL substantially improved both gesture performance accuracy and manual dexterity. The findings point toward an inhibition of interhemispheric rivalry as a potential mechanism of action.
The Protective Roles of PPARα Activation in Triptolide-Induced Liver Injury
Authors: Hu Dan-Dan , Zhao Qi , Cheng Yan , Xiao Xue-Rong , Huang Jian-Feng , Qu Yan , Li Xian , Tang Ying-Mei , Bao Wei-Min , Yang Jin-Hui , Jiang Tao , Hu Jia-Peng , Gonzalez Frank J , Li Fei
Published: June 2019

Triptolide (TP), one of the main active ingredients in Tripterygium wilfordii Hook F, is clinically used to treat immune diseases but is known to cause liver injury. The aim of this study was to investigate the biomarkers for TP-induced hepatotoxicity in mice and to determine potential mechanisms of its liver injury. LC/MS-based metabolomics was used to determine the metabolites that were changed in TP-induced liver injury. The accumulation of long-chain acylcarnitines in serum indicated that TP exposure disrupted endogenous peroxisome proliferator-activated receptor α (PPARα) signaling. Triptolide-induced liver injury could be alleviated by treatment of mice with the PPARα agonist fenofibrate, whereas the PPARα antagonist GW6471 increased hepatotoxicity. Furthermore, fenofibrate did not protect Ppara−/− mice from TP-induced liver injury, suggesting an essential role for the PPARα in the protective effect of fenofibrate. Elevated long-chain acylcarnitines may protect TP-induced liver injury through activation of the NOTCH-NRF2 pathway as revealed in primary mouse hepatocytes and in vivo. In agreement with these observations in mice, the increase in long-chain acylcarnitines was observed in the serum of patients with cholestatic liver injury compared with healthy volunteers. These data demonstrated the role of PPARα and long-chain acylcarnitines in TP-induced hepatotoxicity, and suggested that modulation of PPARα may protect against drug-induced liver injury.
Gestational and Lactational Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Downregulates Junctional Proteins, Thyroid Hormone Receptor α1 Expression, and the Proliferation-Apoptosis Balance in Mammary Glands Post Puberty
Authors: Gouesse Rita-Josiane , Lavoie Mélanie , Dianati Elham , Wade Mike G , Hales Barbara F , Robaire Bernard , Plante Isabelle
Published: June 2019

Mammary gland development requires hormonal regulation during puberty, pregnancy, and lactation. Brominated flame retardants (BFRs) are endocrine disruptors; they are added to consumer products to satisfy flammability standards. Previously, we showed that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts proteins of the adherens junctions in rat dam mammary glands at weaning. Here, we hypothesize that perinatal exposure to the same BFR mixture also disrupts junctional proteins and signaling pathways controlling mammary gland development in pups. Dams were exposed through diet to a BFR mixture based on the substances in house dust; doses of the mixture used were 0, 0.06, 20, or 60 mg/kg/day. Dams were exposed continuously beginning prior to mating until pups’ weaning; female offspring were euthanized on postnatal day (PND) 21, 46, and 208. The lowest dose of BFRs significantly downregulated adherens junction proteins, E-cadherin, and β-catenin, and the gap junction protein p-Cx43, as well as thyroid hormone receptor alpha 1 protein at PND 46. No effects were observed on estrogen or progesterone receptors. The low dose also resulted in a decrease in cleaved caspase-3, a downward trend in PARP levels, proteins involved in apoptosis, and an upward trend in proliferating cell nuclear antigen, a marker of proliferation. No effects were observed on ductal elongation or on the numbers of terminal end buds. Together, our results indicate that gestational and lactational exposure to an environmentally relevant mixture of BFRs disrupts cell-cell interactions, thyroid hormone homeostasis and the proliferation-apoptosis balance at PND 46, a critical stage for mammary gland development.
Pattern of antibiotic prescribing and factors associated with it in eight village clinics in rural Shandong Province, China: a descriptive study
Authors: Yin Jia , Dyar Oliver James , Yang Peng , Yang Ding , Marrone Gaetano , Sun Mingli , Sun Chengyun , Sun Qiang , Lundborg Cecilia Stålsby
Published: June 2019

Background

This study describes the patterns of antibiotic prescribing in eight village clinics in rural China and evaluates factors associated with antibiotic prescribing using quantitative and qualitative methods.

Methods

From January 2015 to July 2017, 60 prescriptions were collected monthly from selected village clinics in Shandong, China. Village clinic doctors completed a questionnaire regarding their knowledge of antibiotic prescribing. Semi-structured interviews were conducted with 15 village doctors and 1 deputy director from the township hospital.

Results

Of the 14 526 prescriptions collected, 5851 (40.3%) contained at least one antibiotic, among which 18.4% had two or more antibiotics and 24.3% had parenteral antibiotics. The antibiotic prescribing rate (β=−0.007 [95% confidence interval −0.009 to −0.004]) showed a declining trend (1.7% per month). Higher antibiotic prescribing rates were observed for patients <45 y of age and those diagnosed with upper respiratory tract infections and among village doctors who had less working experience and a lower level of knowledge on antibiotic prescribing. Qualitative analyses suggested that antibiotic prescribing was influenced by the patients’ symptoms, patients’ requests, policies restraining the overuse of antibiotics, subsidies for referral and routine village doctor training.

Conclusions

Antibiotic prescribing has declined in the included village clinics, which may be due to the policy of reducing antibiotic overuse in primary health care centres in China.
Assessing species boundaries in the open sea: an integrative taxonomic approach to the pteropod genus Diacavolinia
Authors: Burridge Alice K , Van Der Hulst Remy , Goetze Erica , Peijnenburg Katja T C A
Published: June 2019

To track changes in pelagic biodiversity in response to climate change, it is essential to accurately define species boundaries. Shelled pteropods are a group of holoplanktonic gastropods that have been proposed as bio-indicators because of their vulnerability to ocean acidification. A particularly suitable, yet challenging group for integrative taxonomy is the pteropod genus Diacavolinia, which has a circumglobal distribution and is the most species-rich pteropod genus, with 24 described species. We assessed species boundaries in this genus, with inferences based on geometric morphometric analyses of shell-shape variation, genetic (cytochrome c oxidase subunit I, 28S rDNA sequences) and geographic data. We found support for a total of 13 species worldwide, with observations of 706 museum and 263 freshly collected specimens across a global collection of material, including holo‐ and paratype specimens for 14 species. In the Atlantic Ocean, two species are well supported, in contrast to the eight currently described, and in the Indo‐Pacific we found a maximum of 11 species, partially merging 13 of the described species. Distributions of these revised species are congruent with well-known biogeographic provinces. Combining varied datasets in an integrative framework may be suitable for many diverse taxa and is an important first step to predicting species-specific responses to global change.
PREVALENCE AND TIME TRENDS OF MYOPIA IN CHILDREN AND ADOLESCENTS IN CHINA
Authors: Dong Li , Kang Yi Kun , Li Yang , Wei Wen Bin , Jonas Jost B.
Published: June 2019

Purpose:

To estimate prevalence, associated factors, and time trends of myopia in Chinese children and adolescents.

Methods:

We searched PubMed, EMBASE, and Web of Science for studies examining the prevalence of myopia in children and adolescents aged 3 years to 19 years in China before October 2018. We pooled the prevalence and associated factors for myopia and estimated time trends.

Results:

In 22 eligible studies including 192,569 individuals, the pooled prevalence (95% confidence interval [CI]) of myopia and high myopia in the study period from 1998 to 2016 was 37.7% (95% CI: 23.5–52.0%) and 3.1% (95% CI: 1.2–5.0%), respectively, with higher odds for girls than boys (myopia: odds ratio: 1.29; 95% CI: 1.14–1.46; P < 0.001; high myopia: odds ratio: 1.37; 95% CI: 1.05–1.78; P = 0.02) and with higher prevalences for urban areas than rural regions (myopia: 48.8% [95% CI: 32.3–65.3] vs. 31.9% [95% CI: 20.4–43.3; P < 0.001]). The pooled prevalence of myopia and high myopia increased from 4.7% (95% CI: 2.5–6.9) and 0.2% (95% CI: 0.0–0.5), respectively, in <7-years-olds to 56.2% (95% CI: 29.8–82.5) and 15.1% (95% CI: 6.4–23.8), respectively, in 16- to 18-year-olds. Myopic refractive error increased with older age (P < 0.001), female gender (P < 0.001), and study year (P = 0.003). Studies performed after 2013 showed a prevalence of myopia and high myopia in the 16- to 18-year-olds of 84.8% (95% CI: 84.4–85.2%) and 19.3% (95% CI: 18.6–20.2%), respectively. Assuming a further linear relationship with the study year, myopia prevalence in 2050 among children and adolescents aged 3 years to 19 years would be estimated to be about 84%.

Conclusion:

The marked rise in high myopia prevalence among adolescents in China may be of importance for high myopia as risk factor for irreversible vision loss in Chinese adults in the future.
INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUES AND OUTER RETINAL LAYER STRUCTURES
Authors: Faria Mun Yueh , Proença Helena , Ferreira Nuno G. , Sousa David Cordeiro , Neto Eliana , Marques-Neves Carlos
Published: June 2019

Purpose:

To examine the influence of the inverted flap (IF) internal limiting membrane (ILM) technique in macular hole (MH) closure on outer retinal layers after MH surgery.

Methods:

Retrospective study. Postoperative position of ILM, recovery rate of external limiting membrane and ellipsoid zone, and best-corrected visual acuity were evaluated. The Inserted group, where the IF is placed inside the hole, was compared with the Cover group, where the IF completely covers the hole.

Results:

Sixty-two eyes of 58 patients who underwent vitrectomy and ILM peeling with the IF technique for large MHs (>400 µm) with successful MH closure and a follow-up of 12 months were evaluated. In the 24 eyes of the Inserted group, there was no regeneration of external limiting membrane or ellipsoid zone after 12 months. In the 38 eyes of Cover group, external limiting membrane recovered in 55.3% of patients 1 month after surgery, and in 86.1% after 12 months. The elipsoid zone layer was present in 58% of the patients.

Conclusion:

Poorer anatomical and visual results were associated with the IF technique where ILM insertion occurs compared with ILM placed over the hole. These findings suggest that insertion of the ILM in the hole might prevent outer retinal layers realignment and visual recovery in MH surgery.
Electron Microscopic Evidence of Photoreceptor Outer-segments in the Trabecular Meshwork in a Case of Schwartz-Matsuo Syndrome
Authors: Clark Antony , Alkhotani Alaa , Yucel Yeni H. , Sylvester Carly , Kertes Peter J. , Birt Catherine M.
Published: June 2019

Purpose:

To describe a case of photoreceptor outer segment glaucoma (Schwartz-Matsuo syndrome) with electron microscopic evidence of photoreceptor outer segments in the trabecular meshwork (TM).

Design:

This is a clinicopathologic case report.

Participant:

A 48-year-old Filipino man.

Methods:

Specimens of aqueous humor and TM in a clinical case of Schwartz-Matsuo syndrome were examined by electron microscopy.

Main Outcome Measures:

Electron photomicroscopy.

Results:

Electron microscopy showed evidence of retinal photoreceptor outer-segments in both an aqueous humor and a TM specimen.

Conclusion:

Schwartz-Matsuo syndrome is associated with the presence of photoreceptor outer segments in the TM.
Predictive Factors Associated With In-Hospital Mortality for Patients Across the Sepsis Spectrum
Authors: Baccaglini Lorena , Araz Ozgur M. , Naveed Zaeema , Whitsitt Ben , Beachy Micah , Winterboer Tammy , Haynatzki Gleb , Ash Michael
Published: June 2019

Introduction

Sepsis poses a large burden for hospitals across the world owing to its high resource utilization and poor patient outcomes. This project aimed to assess and quantify the importance of sepsis-specific predictors for in-hospital mortality. Several studies have identified comorbidities and clinical laboratory variables associated with mortality among the severe sepsis population, but few have combined the 2 in making a model specific for all sepsis patients.

Methods

We used clinical and laboratory variables seen at the time of first lactic acid measurement and patient characteristics upon admission to develop a logistic regression model to predict mortality in a sepsis population at 2 area hospitals in Omaha, Nebraska.

Results

Overall, sepsis-related mortality was 12.9%. Advanced age, a higher number of comorbidities, and leucopenia were positively associated with mortality, whereas preexisting diabetes was negatively associated with mortality. Each 1 mmol/L difference in lactic acid levels was positively associated with 1.38 times higher adjusted odds (95% confidence interval, 1.30–1.48) of mortality after adjustment for other covariates. For every 1% decrease in hematocrit, the adjusted odds of mortality were 1.04 times higher (95% confidence interval, 1.02–1.06).

Conclusions

We identified a number of sepsis mortality predictors. The negative association between preexisting diabetes mellitus and sepsis mortality requires further investigation.
Microbiological Spectrum of Infection-Related Febrile Episodes in Adult Patients With Hematologic Malignancies
Authors: Miradi Mahdi , Sheybani Fereshte , Sarvghad Mohammad Reza , Allahyari Abolghasem , Arian Mahnaz , Nooghabi Mehdi Jabbari
Published: June 2019

Background

In recent years, antimicrobial resistance and the limited number of new antimicrobials under development have profoundly complicated treatment options especially in patients with hematologic malignancies that are treated with sequential courses of antimicrobial therapy. These issues emphasize on the importance of surveillance studies to monitor antimicrobial resistance and implement the antimicrobial stewardship strategies in health care centers.

Methods

The study was a prospective cohort with the aim of evaluating the microbiological spectrum of infection-related febrile episodes in adult patients with hematologic malignancies who admitted in a 1000-bed teaching hospital affiliated to Mashhad University of Medical Sciences, Iran.

Results

One hundred eight infection-related febrile episodes were identified in 108 individuals with hematologic malignancies of whom 18.5% had bacteremia. The most commonly isolated pathogens were coagulase-negative staphylococci (40%), followed by Escherichia coli (25%), and Klebsiella spp (10%), respectively. Carbapenems and glycopeptides were prescribed in the empirical regimen of 96.4% and 61.2% of patients. Although more than 67% of them needed to be deescalated at the second key time of antimicrobial therapy, it was performed only in 9%.

Conclusions

Our study highlighted the high rates of prescription of broad-spectrum antimicrobials in the empirical regimen of patients and a poor adherence to appropriate deescalation strategies after the second key time point of antimicrobial therapy among physicians in charge of patients with hematologic malignancies. It also emphasizes the importance of developing infrastructure for implementation and adherence to antimicrobial stewardship strategies in hematologic malignancy wards in developing countries such as Iran.
Sepsis, Helicoid Bacteremia, and Pneumatosis Intestinalis
Authors: Lacy Mark D. , Fisher Mark A.
Published: June 2019

Spirochetal or helical configurations are unusual among human pathogens. The number of organisms that will grow in standard blood culture media and stain well with Gram stain is even less common. This is a fatal case of sepsis with pneumatosis intestinalis due to the anaerobic spiral-formed pathogen Anaerobiospirillum succiniciproducens. It is followed by a brief discussion of organisms to consider when the laboratory calls to report “a spirochete is growing in the blood culture” along with a caveat in choosing antimicrobial therapy when A. succiniciproducens is a possibility.

Human pathogens configured as helixes or spirals are comprised by a limited number of genera. Furthermore, most of the pathogens reported in the clinical literature will not stain with Gram stain. This is a case of one such pathogen, which may be included in the differential diagnosis of the prudent infectious disease specialist when told by the microbiology laboratory, “we see spirochetes on the gram stain of the blood culture.”
Preseason Vestibular Ocular Motor Screening in Children and Adolescents
Authors: Iverson Grant L. , Cook Nathan E. , Howell David R. , Collings Laurel J. , Kusch Cody , Sun Jonathan , Virji-Babul Naznin , Panenka William J.
Published: June 2019

Objectives:

The primary purpose of this study was to examine vestibular/ocular motor screening (VOMS) test performance in a sample of healthy youth ice hockey players. A particular focus was to investigate the potential effects of age and pre-existing health conditions, including concussion history, attention-deficit/hyperactivity disorder (ADHD), learning disability (LD), headaches/migraines, and depression/anxiety on preseason baseline VOMS performance, including the near point of convergence (NPC) distance.

Design:

Cross-sectional cohort.

Setting:

Outpatient physiotherapy clinic.

Participants:

Three hundred eighty-seven male youth hockey players, with an average age of 11.9 years (SD = 2.2, range = 8-17), completed the VOMS and responded to self- or parent-reported demographic and medical history questionnaires during preseason baseline assessments.

Independent Variables Assessed:

Age, sex, and mental and physical health history including ADHD, headaches, depression, anxiety, migraine, and LD.

Outcome Measure:

Vestibular/ocular motor screening.

Results:

The large majority of boys scored within normal limits on the VOMS, ie, they reported no symptom provocation of more than 2 points on any VOMS subset (89%) and had a normal NPC distance, ie, <5 cm (78%). The individual VOMS subtests had low abnormality rates, and demographic and pre-existing health conditions, such as age, headache or migraine history, previous neurodevelopmental conditions, or mental health problems, were not associated with clinically meaningful symptom provocation during the VOMS.

Conclusions:

There was a low rate of abnormal findings for the individual VOMS subtests, with the exception of NPC distance, among male youth hockey players during preseason assessment.
Syrian Refugees and Their Impact on Health Service Delivery in the Pediatric Hematology/Oncology Clinics Across Canada
Authors: Barry Rachid M. , Chretien Christine , Kirby Melanie , Gallant Gloria , Leppington Sarah , Robitaille Nancy , Corriveau-Bourque Catherine , Stoffman Jayson , Wu John , Leaker Michael , Klaassen Robert J.
Published: June 2019

This study examined the impact of Syrian refugees on 1 area of the Canadian health care sector. We predicted that pediatric hematology clinics across Canada would see a spike in their Syrian refugee patient population in proportion to their recent migration and, as a result, an increase in perceived workload. Data on the number of refugee patients, types of diseases, and perceived workload were gathered from hematology clinics across Canada using a clinical survey (Supplemental Digital Content 1, http://links.lww.com/JPHO/A315). The results showed that Ontario had the most Syrian refugee patients, followed by the Quebec, Western Canadian, and Atlantic regions. The results also showed that perceived workload ranged from “no increase” (4 programs) to “minimal increase” <25% (1 program), “moderate increase” 25% to 75% (4 programs), and “significant increase” >75% (3 programs, 2 of which had no transfusion-dependent thalassemia patients before the immigration).
Understanding Gunshot Residue Evidence and Its Role in Forensic Science
Authors: Vachon Crystina R. , Martinez Michael V.
Published: June 2019

Gunshot residue, or GSR, can be a valuable tool in forensic science, but its importance depends greatly on how it is utilized during an investigation and applied in criminal courts. This comprehensive review defines what constitutes GSR resulting from a discharged firearm. Sampling methods and analytical testing instrumentation will be discussed along with data interpretation and limitations of analysis.
Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations
Authors: Farnung Lucas , Ochmann Moritz , Cramer Patrick
Published: June 2019

Chromatin remodelling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at super-helical location (SHL) +2, supporting the ‘twist defect’ model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our results also rationalize the effect of CHD4 mutations that are associated with cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.
Development of a Genomic DNA Reference Material Panel for Thalassemia Genetic Testing
Authors: Yin Zhen-Zhen , Qu Shou-Fang , Huang Chuan-Feng , Chen Fang , Li Jian-Biao , Chen Shi-Ping , Zheng Yu , Zhang Xi , Yang Xue-Xi , Xie Long-Xu , Wei Ji-Tao , Wei Feng-Xiang , Guo Jian , Huang Jie
Published: June 2019

Thalassemia is one of the most common autosomal recessive inherited diseases worldwide, and it is also highly prevalent and variable in Southern China. Various types of genetic testing technologies have been developed for diagnosis and screening of thalassemia. Characterized genomic DNA reference materials are necessary for assay development, validation, proficiency testing and quality assurance. However, there is no publicly available reference materials for thalassemia genetic testing as yet. To address the need for these materials, the National Institutes for Food and Drug Control and the China National Gene Bank established 31 new cell lines with 2 wild genotypes and 29 distinct genotypes of thalassemia which account for approximately 90% thalassemia carriers in China. The genomic DNA of 31 cell lines were characterized by four clinical genetic testing laboratories using different genetic testing methods and technology platforms. The genotyping results were concordant among four laboratories. In addition, the results of stability test demonstrated that the genotypes of these DNA samples were not influenced by preanalytical conditions such as long-term exposure to high temperature(37□) environment and repeated freeze-thawing. In conclusion, we developed the first national panel of 31 genomic DNA reference materials which are renewable and publicly available for the quality assurance of various genetic testing methods and will facilitate research and development in thalassemia genetic testing.
Regression from pathological hypertrophy is sexually dimorphic and stimulus-specific
Authors: Muehleman Deanna , Swearingen Alison R. , Leinwand Leslie A.
Published: June 2019

Aims

Pathological cardiac hypertrophy is the result of increased cardiomyocyte size, leading to thickening of the left ventricular walls and a decrease in the left ventricular chamber. With early treatment of the underlying cause, cardiac hypertrophy can be reversed in some individuals, while it persists in others. Here, we investigate mechanisms leading to regression of pathological cardiac hypertrophy in two mouse models, in addition to defining the sex differences associated with hypertrophy and regression.

Methods and Results

Two pathological hypertrophic stimuli were used in male and female mice (Isoproterenol or Angiotensin II). The stimulus was removed after 7 days of treatment, then the left ventricle was studied at intervals up to 7 days following the removal of the stimulus. Following Isoproterenol removal, male hearts returned to baseline sizes in 4 days while it took 7 days for female hearts to regress. After Angiotensin II removal, the left ventricular masses of males and females did not regress. ERK1/2 was activated in response to both Isoproterenol and Angiotensin II in males, then decreased back to baseline one day after stimulus removal. Expression of ECM genes was greater in response to Angiotensin II and remained elevated longer after Angiotensin II removal, compared to Isoproterenol. Further, collagen content may be playing a role in the irreversible state of Angiotensin II induced hypertrophy as hydroxyproline content was increased following the removal of Angiotensin II in both males and females.

Conclusions

Regression of pathological cardiac hypertrophy is possible in some people and in some mouse models; however, the ability for the heart to regress is dependent on the stimulus and biological sex. Further, molecular changes including cellular signaling, protein degradation pathways and the formation of a fibrotic network may contribute to the ability to reverse pathological cardiac hypertrophy and are stimulus- and sex-dependent.

Translational Perspective

Pathological cardiac hypertrophy is a major risk factor for mortality. If cardiac hypertrophy persists for an extended time, there can be many maladaptive changes to the myocardium. With early treatment of the underlying cause, cardiac hypertrophy can be reversed in some individuals, but not in others. While cardiac hypertrophy has been studied extensively, very little is understood about regression of cardiac hypertrophy. It is important that we have a better understanding of mechanisms leading to regression and why this process might not be reversible in some individuals.