bluuebunny/crossref_metadata_2025 huggingface dataset:
The Synthesis of Copper-doped Hematite Nanoparticles of Iron Ore through Impregnation Method for Photodegradation of Textile Dyes
Authors: Lubis S , Khairi  , Al Haitami I H , Murisna
Published: June 2019

Copper-doped hematite (Cu-doped α-Fe2O3) nanoparticles have been synthesized by the impregnation method using iron ore as the hematite source. The structural and morphological properties of the prepared samples were studied using X-ray diffraction (XRD), scanning electron microscopy (SEM), and nitrogen adsorption-desorption. The XRD results showed that the hematite extracted from iron ore was in the hematite phase. The average crystallite size of copper-doped hematite was slightly smaller than that of hematite. The copper-doped hematite nanoparticles exhibited high photocatalytic activity on degradation of indigo carmine (IC) dye with the degradation percentage of 98.21 % and 99.78%, respectively under UV and solar light irradiation. The highest photocatalytic activity was obtained at the experimental condition namely initial pH of IC solution 1.0, photocatalyst mass of 400 mg, initial concentration dye solution of 15 mg/L, and 90 minutes of irradiation times. The copper-doped hematite nanoparticles could also remove dyes found in batik wastewater with a percentage of the degradation up to 77.56 % and 97.83% under UV and solar light irradiation, respectively.
The Effect of Guava on the Improvement of Lipid Profile in Hypercholesterolemic Rats
Authors: Maryanto Sugeng , Marsono Yustinus
Published: June 2019

Red guava is a fruit species with high vitamin C content and the highest fibers, in particular, soluble fiber (pectin) among tropical fruits and cereals. The soluble fiber is hypocholesterolemic in the body. Therefore, it has the potential to reduce cholesterol content. This study aimed to assess the potential of red guava in reducing cholesterol content in hypocholesterolemic rats. This study applied a pure experiment using a randomized pretestposttest group design on hypocholesterolemic Sprague Dawley rats. The rats were fed with 0.72 g of red guava and pectin supplement as a comparison. The total cholesterol content, LDL, HDL and triglyceride were measured by CHOD-PAP and GPO-PAP methods. Data analysis used t-test and ANOVA with significance rate of 0.05. Red guava intake to the hypocholesterolemic rats significantly reduced the contents of: total cholesterol to 57.8 mg/dL (32%), LDL to 25.5 mg/dL (43%), triglyceride to 19.7 mg/dL (18%). Conversely, it significantly increased HDL content to 10.6 mg/dL (18%). The red guava has proven to give hypocholesterolemic effect by reducing the total cholesterol LDL and triglyceride; Conversely, it significantly increased HDL.
Object files and unconscious perception: a reply to Quilty-Dunn
Authors: Phillips Ian
Published: June 2019

A wealth of cases – most notably blindsight and priming under inattention or suppression – have convinced philosophers and scientists alike that perception occurs outside awareness. In recent work (Phillips 2016a, 2018; Phillips and Block 2017, Peters et al. 2017), I dispute this consensus, arguing that any putative case of unconscious perception faces a dilemma. The dilemma divides over how absence of awareness is established. If subjective reports are used, we face the problem of the criterion: the concern that such reports underestimate conscious experience (Eriksen 1960, Holender 1986, Peters and Lau 2015). If objective measures are used, we face the problem of attribution: the concern that the case does not involve genuine individual-level perception. Quilty-Dunn (2019) presents an apparently compelling example of unconscious perception due to Mitroff et al. (2005) which, he contends, evades this dilemma. The case is fascinating. However, as I here argue, it does not escape the dilemma’s clutches.
Rhinoplasty: A Sequential Approach to Managing the Bony Vault
Authors: Zholtikov Vitaly , Golovatinsky Vladimir , Palhazi Peter , Gerbault Olivier , Daniel Rollin K
Published: June 2019

Background

An important element of most rhinoplasty surgeries is the treatment of the nasal bones, which involves various combinations of osteotomies and hump removal.

Objectives

The aim of this paper was to describe a rhinoplasty technique in which piezoelectric instruments (PEIs) are used to shape nasal bones, with the priority being to preserve the stability of these bones. In most clinical cases, nasal bones can be stabilized if rhinosculpture (RS) is applied broadly, both separately and in combination with different osteotomies, while preserving the nasal bridge.

Methods

A step-by-step algorithm was applied to achieve the required aesthetic results when working with PEIs on the bony pyramid, depending on the degree of asymmetry. We used the fully open approach in all clinical cases, which provided the greatest visual field when performing all the steps involved in treating the bony pyramid, thus fully exploiting all the possibilities and advantages of PEIs.

Results

We report our experience with 165 clinical cases performed over 18 months from December 2016 to July 2018. The patients were divided into 5 groups, depending on the algorithm selected to treat the bony pyramid.

Conclusions

When working with the bony pyramid, our approach limits patient movement, thus ensuring stability of the side walls of the bones in both the short and the long term—a property that greatly improves the aesthetic results.

Level of Evidence: 4
CYP46A1 gene therapy deciphers the role of brain cholesterol metabolism in Huntington’s disease
Authors: Kacher Radhia , Lamazière Antonin , Heck Nicolas , Kappes Vincent , Mounier Coline , Despres Gaëtan , Dembitskaya Yulia , Perrin Elodie , Christaller Wilhelm , Sasidharan Nair Satish , Messent Valérie , Cartier Nathalie , Vanhoutte Peter , Venance Laurent , Saudou Frédéric , Néri Christian , Caboche Jocelyne , Betuing Sandrine
Published: June 2019

Dysfunctions in brain cholesterol homeostasis have been extensively related to brain disorders. The main pathway for brain cholesterol elimination is its hydroxylation into 24S-hydroxycholesterol by the cholesterol 24-hydrolase, CYP46A1. Increasing evidence suggests that CYP46A1 has a role in the pathogenesis and progression of neurodegenerative disorders, and that increasing its levels in the brain is neuroprotective. However, the mechanisms underlying this neuroprotection remain to be fully understood. Huntington’s disease is a fatal autosomal dominant neurodegenerative disease caused by an abnormal CAG expansion in huntingtin’s gene. Among the multiple cellular and molecular dysfunctions caused by this mutation, altered brain cholesterol homeostasis has been described in patients and animal models as a critical event in Huntington’s disease. Here, we demonstrate that a gene therapy approach based on the delivery of CYP46A1, the rate-limiting enzyme for cholesterol degradation in the brain, has a long-lasting neuroprotective effect in Huntington’s disease and counteracts multiple detrimental effects of the mutated huntingtin. In zQ175 Huntington’s disease knock-in mice, CYP46A1 prevented neuronal dysfunctions and restored cholesterol homeostasis. These events were associated to a specific striatal transcriptomic signature that compensates for multiple mHTT-induced dysfunctions. We thus explored the mechanisms for these compensations and showed an improvement of synaptic activity and connectivity along with the stimulation of the proteasome and autophagy machineries, which participate to the clearance of mutant huntingtin (mHTT) aggregates. Furthermore, BDNF vesicle axonal transport and TrkB endosome trafficking were restored in a cellular model of Huntington’s disease. These results highlight the large-scale beneficial effect of restoring cholesterol homeostasis in neurodegenerative diseases and give new opportunities for developing innovative disease-modifying strategies in Huntington’s disease.
Gender Differences in Connectome-based Predictions of Individualized Intelligence Quotient and Sub-domain Scores
Authors: Jiang Rongtao , Calhoun Vince D , Fan Lingzhong , Zuo Nianming , Jung Rex , Qi Shile , Lin Dongdong , Li Jin , Zhuo Chuanjun , Song Ming , Fu Zening , Jiang Tianzi , Sui Jing
Published: June 2019

Scores on intelligence tests are strongly predictive of various important life outcomes. However, the gender discrepancy on intelligence quotient (IQ) prediction using brain imaging variables has not been studied. To this aim, we predicted individual IQ scores for males and females separately using whole-brain functional connectivity (FC). Robust predictions of intellectual capabilities were achieved across three independent data sets (680 subjects) and two intelligence measurements (IQ and fluid intelligence) using the same model within each gender. Interestingly, we found that intelligence of males and females were underpinned by different neurobiological correlates, which are consistent with their respective superiority in cognitive domains (visuospatial vs verbal ability). In addition, the identified FC patterns are uniquely predictive on IQ and its sub-domain scores only within the same gender but neither for the opposite gender nor on the IQ-irrelevant measures such as temperament traits. Moreover, females exhibit significantly higher IQ predictability than males in the discovery cohort. This findings facilitate our understanding of the biological basis of intelligence by demonstrating that intelligence is underpinned by a variety of complex neural mechanisms that engage an interacting network of regions—particularly prefrontal–parietal and basal ganglia—whereas the network pattern differs between genders.
A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa–coendemic Areas: Cost Analysis of a Pilot in the Soa Health District, Cameroon
Authors: Lenk Edeltraud J , Moungui Henri C , Boussinesq Michel , Kamgno Joseph , Nana-Djeunga Hugues C , Fitzpatrick Christopher , Peultier Anne-Claire M M , Klion Amy D , Fletcher Daniel A , Nutman Thomas B , Pion Sébastien D , Niamsi-Emalio Yannick , Redekop William K , Severens Johan L , Stolk Wilma A
Published: June 2019

Background

Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon.

Methods

Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically.

Results

The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9–$3.6), US$5.2 ($4.5–$8.3), and US$5.4 ($4.6–$8.6), respectively.

Conclusions

TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.
Neutralization of CXCL12 attenuates established pulmonary hypertension in rats
Authors: Bordenave Jennifer , Thuillet Raphaël , Tu Ly , Phan Carole , Cumont Amélie , Marsol Claire , Huertas Alice , Savale Laurent , Hibert Marcel , Galzi Jean-Luc , Bonnet Dominique , Humbert Marc , Frossard Nelly , Guignabert Christophe
Published: June 2019

Aims 

The progressive accumulation of cells in pulmonary vascular walls is a key pathological feature of pulmonary arterial hypertension (PAH) that results in narrowing of the vessel lumen, but treatments targeting this mechanism are lacking. The C-X-C motif chemokine 12 (CXCL12) appears to be crucial in these processes. We investigated the activity of two CXCL12 neutraligands on experimental pulmonary hypertension (PH), using two complementary animal models.

Methods and results 

Male Wistar rats were injected with monocrotaline (MCT) or were subjected to SU5416 followed by 3-week hypoxia to induce severe PH. After PH establishment, assessed by pulsed-wave Doppler echocardiography, MCT-injected or SU5416 plus chronic hypoxia (SuHx) rats were randomized to receive CXCL12 neutraligands chalcone 4 or LIT-927 (100 mg/kg/day), the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100 (5 mg/kg/day), or vehicle, for 2 or 3 weeks, respectively. At the end of these treatment periods, echocardiographic and haemodynamic measurements were performed and tissue samples were collected for protein expression and histological analysis. Daily treatment of MCT-injected or SuHx rats with established PH with chalcone 4 or LIT-927 partially reversed established PH, reducing total pulmonary vascular resistance, and remodelling of pulmonary arterioles. Consistent with these observations, we found that neutralization of CXCL12 attenuates right ventricular hypertrophy, pulmonary vascular remodelling, and decreases pulmonary artery smooth muscle cell (PA-SMC) proliferation in lungs of MCT-injected rats and SuHx rats. Importantly, CXCL12 neutralization with either chalcone 4 or LIT-927 inhibited the migration of PA-SMCs and pericytes in vitro with a better efficacy than AMD3100. Finally, we found that CXCL12 neutralization decreases vascular pericyte coverage and macrophage infiltration in lungs of both MCT-injected and SuHx rats.

Conclusion 

We report here a greater beneficial effect of CXCL12 neutralization vs. the conventional CXCR4 blockade with AMD3100 in the MCT and SuHx rat models of severe PH, supporting a role for CXCL12 in the progression of vascular complications in PH and opening to new therapeutic options.
Silvicultural implications from analyzing light induced height growth development of eight North American juvenile tree species in mixed-conifer forests
Authors: Annighöfer Peter , Seidel Dominik , Ammer Christian , Stephens Scott L , York Robert A
Published: June 2019

Modern silviculture is based on simulating natural disturbance regimes on the one side and reducing their impact on the other side. Disturbances modify light regimes of forests along complex spatial patterns, and species participating in the ecosystem tend to have unique adaptations to the multitude of light conditions found in forests. We studied the height growth reaction of saplings from eight native North American tree species to different light availabilities in a Sierra Nevada mixed conifer forest. Large height growth differences occurred between species. Height growth increased for most species with increasing light availability. However, black oak but also incense cedar and tanoak reached an optimal value or saturation point of light availability at intermediate light levels, above which their growth stayed the same or slightly declined on average. A variety of stand conditions, representing the range from early to late successional stages, are beneficial to maintain tree species diversity across stands. Such a gradient of conditions can be achieved by diversifying silvicultural regimes and using regeneration approaches that mimic a range of disturbance intensities. The results add to knowledge on the species’ ecology by specifying their height growth in dependence of a quantified light environment. The quantification of the light environment can directly be linked to % canopy cover and a range of regeneration methods, respectively. With this, the results may help achieve a more precise and target-oriented management of Sierra Nevada mixed conifer forests.
Exhibiting Work in Germany—From Industrial Labour to (Industrial) Culture*
Authors: Kritter Sabine
Published: June 2019

History museums in old industrial regions are important agents in the current debate on how we perceive work in our society. One of their key issues is how work built the region and how it changed in the context of deindustrialization. The article explores the depictions of work in the Ruhr Museum, which is the central regional history museum of the foremost region of heavy industry in Germany. It shows that with few exceptions the representations of the past in this museum include only images of standardized male industrial work, mainly in the coal and steel industries. Furthermore, it demonstrates that in the sections of the museum dedicated to the present, work has disappeared almost entirely from the representations, to be replaced with representations of culture, including industrial heritage, and lifestyles. In light of these findings the article argues that this way of presenting (and not presenting) work emphasizes the break between the past and the present. It homogenizes the historical narrative of work while making current work forms invisible and downplaying the continuing importance of the world of work. Instead, the museum tells a story of loss that requires compensation by culture.
Concurrent Western Australian telephone surveys highlight the advantages of sampling from a registry of recreational fishers
Authors: Taylor S M , Ryan K L
Published: June 2019

Surveys play an integral role in providing reliable recreational fishing information for the sustainable management of fisheries resources. The selection of a representative sample is an important and often challenging part of designing surveys. Here we compare concurrent telephone surveys conducted in 2016 and 2017 using a telephone directory (White Pages®, WP) and a Recreational Boat Fishing Licence (RBFL) as sampling frames. Information on boat- and shore-based recreational fishing was collected from both surveys. The response rates for the RBFL surveys were more than double those from the WP surveys. The RBFL surveys identified more respondents who had recreationally fished in the previous 12 months compared to the WP surveys. Fishing activity differed markedly between fishers in the WP and RBFL surveys; however, characteristics were consistent for boat-based fishers sampled from the two types of surveys. The high levels of sample loss observed in the WP surveys suggest that other general population lists may provide greater coverage of shore-based fishers. We recommend testing the demographic and behavioural characteristics of recreational fishers sampled in offsite surveys against benchmark data to assist in assessing whether or not the characteristics of the sample are representative of the target population.
Bivalent Human Papillomavirus (HPV) Vaccine Effectiveness Correlates With Phylogenetic Distance From HPV Vaccine Types 16 and 18
Authors: Bogaards Johannes A , van der Weele Pascal , Woestenberg Petra J , van Benthem Birgit H B , King Audrey J
Published: June 2019

To substantiate cross-protection reported across AS04-adjuvanted bivalent human papillomavirus (HPV) vaccine (2vHPV) studies, we reevaluated vaccine effectiveness against type-specific HPV positivity as a function of phylogenetic distance to vaccine target types HPV-16 and -18. We provide evidence of sustained cross-protection up to 8 years postvaccination in a high-risk population in the Netherlands. Moreover, our findings suggest that genomic distance better explains cross-protection than distance measures based on capsid antigens only. Taken together, 2vHPV is predicted to provide partial cross-protection against HPV-31, -33, -35, -45, -52, and possibly -58, that is, acknowledged oncogenic types with close phylogenetic relationships to HPV-16 or -18.
Leisure-Time Music Groups and Their Localities: Exploring the Commercial, Educational, and Reciprocal Relationships of Amateur Music-Making
Authors: Pitts Stephanie E
Published: June 2019

Membership of an amateur musical group is typically understood in relation to members’ experiences: the research undertaken for this article poses new questions about the ways in which those groups connect with other people, organizations, and venues in their locality to build a broader sense of culturally engaged citizenship. The networks built by amateur musicians are often rendered invisible in the research literature and in policy-making in ways that limit the understanding and recognition of their contribution to contemporary society. Through a collaboration with the national network Making Music, the commercial, educational, and reciprocal relationships of a particular variety of amateur music-making are revealed. This article presents a new framework for understanding organized amateur musical engagement as part of a cultural ecology, and considers the implications for recognizing and supporting leisure-time music groups.
CRISPR/Cas9-targeted removal of unwanted sequences from small-RNA sequencing libraries
Authors: Hardigan Andrew A , Roberts Brian S , Moore Dianna E , Ramaker Ryne C , Jones Angela L , Myers Richard M
Published: June 2019

In small RNA (smRNA) sequencing studies, highly abundant molecules such as adapter dimer products and tissue-specific microRNAs (miRNAs) inhibit accurate quantification of lowly expressed species. We previously developed a method to selectively deplete highly abundant miRNAs. However, this method does not deplete adapter dimer ligation products that, unless removed by gel-separation, comprise most of the library. Here, we have adapted and modified recently described methods for CRISPR/Cas9–based Depletion of Abundant Species by Hybridization (‘DASH’) to smRNA-seq, which we have termed miRNA and Adapter Dimer—DASH (MAD-DASH). In MAD-DASH, Cas9 is complexed with single guide RNAs (sgRNAs) targeting adapter dimer ligation products, alongside highly expressed tissue-specific smRNAs, for cleavage in vitro. This process dramatically reduces adapter dimer and targeted smRNA sequences, can be multiplexed, shows minimal off-target effects, improves the quantification of lowly expressed miRNAs from human plasma and tissue derived RNA, and obviates the need for gel-separation, greatly increasing sample throughput. Additionally, the method is fully customizable to other smRNA-seq preparation methods. Like depletion of ribosomal RNA for mRNA-seq and mitochondrial DNA for ATAC-seq, our method allows for greater proportional read-depth of non-targeted sequences.
MTR-Viewer: identifying regions within genes under purifying selection
Authors: Silk Michael , Petrovski Slavé , Ascher David B
Published: June 2019

Advances in genomic sequencing have enormous potential to revolutionize personalized medicine, however distinguishing disease-causing from benign variants remains a challenge. The increasing number of human genome and exome sequences available has revealed areas where unfavourable variation is removed through purifying selection. Here, we present the MTR-Viewer, a web-server enabling easy visualization at the gene or variant level of the Missense Tolerance Ratio (MTR), a measure of regional intolerance to missense variation calculated using variation from 240 000 exome and genome sequences. The MTR-Viewer enables exploration of MTR calculations, using different sliding windows, for over 18 000 human protein-coding genes and 85 000 alternative transcripts. Users can also view MTR scores calculated for specific ethnicities, to enable easy exploration of regions that may be under different selective pressure. The spatial distribution of population and known disease variants is also displayed on the protein's domain structure. Intolerant regions were found to be highly enriched for ClinVar pathogenic and COSMIC somatic missense variants (Mann–Whitney U test P < 2.2 × 10−16). As the MTR is not biased by known domains and protein features, it can highlight functionally important regions within genes overlooked or inaccessible by traditional methods. MTR-Viewer is freely available via a user friendly web-server at http://biosig.unimelb.edu.au/mtr-viewer/.
Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase
Authors: Jackson Lynnette N , Chim Nicholas , Shi Changhua , Chaput John C
Published: June 2019

Replicative DNA polymerases are highly efficient enzymes that maintain stringent geometric control over shape and orientation of the template and incoming nucleoside triphosphate. In a surprising twist to this paradigm, a naturally occurring bacterial DNA polymerase I member isolated from Geobacillus stearothermophilus (Bst) exhibits an innate ability to reverse transcribe RNA and other synthetic congeners (XNAs) into DNA. This observation raises the interesting question of how a replicative DNA polymerase is able to recognize templates of diverse chemical composition. Here, we present crystal structures of natural Bst DNA polymerase that capture the post-translocated product of DNA synthesis on templates composed entirely of 2′-deoxy-2′-fluoro-β-d-arabino nucleic acid (FANA) and α-l-threofuranosyl nucleic acid (TNA). Analysis of the enzyme active site reveals the importance of structural plasticity as a possible mechanism for XNA-dependent DNA synthesis and provides insights into the construction of variants with improved activity.
Study of conformational transitions of i-motif DNA using time-resolved fluorescence and multivariate analysis methods
Authors: Benabou Sanae , Ruckebusch Cyril , Sliwa Michel , Aviñó Anna , Eritja Ramon , Gargallo Raimundo , de Juan Anna
Published: June 2019

Recently, the presence of i-motif structures at C-rich sequences in human cells and their regulatory functions have been demonstrated. Despite numerous steady-state studies on i-motif at neutral and slightly acidic pH, the number and nature of conformation of this biological structure are still controversial. In this work, the fluorescence lifetime of labelled molecular beacon i-motif-forming DNA sequences at different pH values is studied. The influence of the nature of bases at the lateral loops and the presence of a Watson–Crick-stabilized hairpin are studied by means of time-correlated single-photon counting technique. This allows characterizing the existence of several conformers for which the fluorophore has lifetimes ranging from picosecond to nanosecond. The information on the existence of different i-motif structures at different pH values has been obtained by the combination of classical global decay fitting of fluorescence traces, which provides lifetimes associated with the events defined by the decay of each sequence and multivariate analysis, such as principal component analysis or multivariate curve resolution based on alternating least squares. Multivariate analysis, which is seldom used for this kind of data, was crucial to explore similarities and differences of behaviour amongst the different DNA sequences and to model the presence and identity of the conformations involved in the pH range of interest. The results point that, for i-motif, the intrachain contact formation and its dissociation show lifetimes ten times faster than for the open form of DNA sequences. They also highlight that the presence of more than one i-motif species for certain DNA sequences according to the length of the sequence and the composition of the bases in the lateral loop.
Flights to Safety
Authors: Baele Lieven , Bekaert Geert , Inghelbrecht Koen , Wei Min
Published: June 2019

We identify flight-to-safety (FTS) days for twenty-three countries using only stock and bond returns and a model averaging approach. FTS days comprise less than 2% of the sample and are associated with a 2.7% average bond-equity return differential and significant flows out of equity funds and into government bond and money market funds. FTS represents flights to both quality and liquidity in international equity markets, but mainly a flight to quality in the U.S. corporate bond market. Emerging markets, endowment funds, and hedge funds perform poorly during FTS, whereas hedge funds appear to vary their systematic exposures prior to an FTS.

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.
THE DETERMINATION OF NEUTRON FLUENCE TO ABSORBED DOSE CONVERSION COEFFICIENTS AND RELATIVE BIOLOGICAL EFFECT BASED ON MICRODOSIMETRY MEASUREMENTS
Authors: Zhang Weihua , Li Chunjuan , Zou Yisheng , Liu Yina , Luo Hailong
Published: June 2019

A tissue-equivalent proportional counter (TEPC) is a reference detector to measure microdosimetric quantities. A conventional spherical TEPC and a novel TEPC based on a ceramic thick gas electron multiplier (THGEM) foil were developed to carry out microdosimetric measurements of lineal energy spectra in monoenergetic and 252Cf/241Am-Be neutron radiation fields, and the absorbed dose values had been derived. In order to go further in radiobiology and therapy, the fluence to absorbed dose conversion coefficients in neutron fields were also determined. According to the dose distribution in lineal energy, the neutron relative biological effect (RBE) values were also calculated using an empirical procedure applying biological weighting functions.
Total Health Care Expenditure in Patients With a Herniated Lumbar Disk That Ultimately Require Surgery
Authors: Davison Mark A. , Lilly Daniel T. , Moreno Jessica , Bagley Carlos , Adogwa Owoicho
Published: June 2019

Study Design:

A retrospective cohort study.

Objective:

To compare the cost of maximum nonoperative therapy (MNT) in patients diagnosed with a herniated lumbar disk undergoing primary (1–3 mo) versus prolonged (4–6 mo) conservative management before microdiscectomy.

Summary of Background Data:

Patients diagnosed with a herniated lumbar disk often attempt a 3-month trial of conservative management before microdiscectomy. A paucity of data exists characterizing the cost of a subsequent round of nonoperative therapies in patients who fail their initial trial, rather than undergo surgery.

Methods:

Clinical records from patients diagnosed with a herniated lumbar disk undergoing index microdiscectomy surgery from 2007 to 2017 were gathered from a large insurance database. Records were searchable by International Classification of Diseases diagnosis/procedure codes, Current Procedural Terminology codes, and generic drug codes. Two cohorts were established: patients undergoing primary (1–3 mo) versus prolonged (4–6 mo) courses of conservative management. Nonoperative therapy utilization was documented from initial herniation diagnosis to microdiscectomy surgery. “Utilization” encompassed cost billed to patients, prescriptions written, and quantity of units dispensed.

Results:

The 3-month MNT cohort included 4587 patients and the 6-month MNT cohort contained 1506 patients. A greater percentage of 6-month cohort patients utilized opioids (P=0.0052), muscle relaxants (P=0.0061), and lumbar steroid injections (P<0.0001). When considering the average amount spent on conservative management, 6-month patients ($1824/patient) spent 1.55 times more than 3-month patients ($1178/patient). The 6-month:3-month average spending ratio was <2.0 for all of the nonoperative therapies except nonsteroidal anti-inflammatory drugs (2.66) and epidural steroid injections (2.25). When normalized by the number of opioid users, the number of opioid medications dispensed was proportionally less in 3-month patients compared with 6-month patients, with a 6-month:3-month ratio of 1.52.

Conclusions:

The costs associated with a subsequent course of nonoperative therapies for symptomatic lumbar disk herniation seem to be slightly less than that of the primary trial. Assuming a minimal clinical benefit after the initial trial of nonsurgical therapies, the incremental cost-effectiveness ratio of a subsequent trial versus surgery may be unfavorable. Future studies identifying patients likely to benefit from surgery earlier in the treatment course is required.

Level of Evidence:

Level III.
A Nano-Dose Protocol For Cobb Angle Assessment in Children With Scoliosis: Results of a Phantom-based and Clinically Validated Study
Authors: Pedersen Peter H. , Vergari Claudio , Tran Alexia , Xavier Fred , Jaeger Antoine , Laboudie Pierre , Housset Victor , Eiskjær Søren P. , Vialle Raphäel
Published: June 2019

Study design:

This was a prospective validation study with technical notes.

Objective:

This study aimed to validate a new ultra–low-dose full-spine protocol for reproducible Cobb angle measurements—the “nano-dose” protocol.

Summary of Background Data:

Scoliosis is a 3-dimensional (3D) deformity of the spine characterized by 3D clinical parameters. Nevertheless, 2D Cobb angle remains an essential and widely used radiologic measure in clinical practice. Repeated imaging is required for the assessment and follow-up of scoliosis patients. The resultant high dose of absorbed radiation increases the potential risk of developing radiation-induced cancer in such patients. Micro-dose radiographic imaging is already available in clinical practice, but the radiation dose delivered to the patient could be further reduced.

Methods:

An anthropomorphic child phantom was used to establish an ultra–low-dose protocol in the EOS Imaging System still allowing Cobb angle measurements, defined as nano-dose. A group of 23 consecutive children presenting for scoliosis assessment, 12 years of age or younger, were assessed with standard-dose or micro-dose and additional nano-dose full-spine imaging modalities. Intraobserver and interobserver reliability of determining the reliability of 2D Cobb angle measurements was performed. The dosimetry was performed in the anthropomorphic phantom to confirm theoretical radiation dose reduction.

Results:

A nano-dose protocol was established for reliable Cobb angle measurements. Dose area product with this new nano-dose protocol was reduced to 5 mGy×cm2, corresponding to one sixth of the micro-dose protocol (30 mGy×cm2) and <1/40th of the standard-dose protocol (222 mGy×cm2). Theoretical dose reduction, for posteroanterolateral positioning was confirmed using phantom dosimetry. Our study showed good reliability and repeatability between the 2 groups. Cobb variability was <5 degrees from the mean using 95% confidence intervals.

Conclusions:

We propose a new clinically validated nano-dose protocol for routine follow-up of scoliosis patients before surgery, keeping the radiation dose at a bare minimum, while allowing for reproducible Cobb angle measurements.
Safety and Effectiveness of Antifibrinolytics in Posterior Scoliosis Surgery for Adolescent Idiopathic Scoliosis
Authors: Bovonratwet Patawut , Sheha Evan D. , Ondeck Nathaniel T. , Malpani Rohil , Smith Brian G. , Grauer Jonathan N.
Published: June 2019

Study Design:

This was a retrospective study of prospectively collected data.

Objective:

To utilize a large national database with prospectively collected data [National Surgical Quality Improvement Program Pediatric (NSQIP-Pediatric)] to study the safety and effectiveness of antifibrinolytic use during multilevel posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS).

Summary of Background Data:

There is currently a lack of consensus and evidence regarding the safety and effectiveness of antifibrinolytic use for pediatric patients undergoing corrective surgery for AIS.

Materials and Methods:

Patients who underwent multilevel PSF for AIS in the 2016 NSQIP-Pediatric database were identified. Preoperative and procedural characteristics were compared between patients who received antifibrinolytics versus those who did not. Multivariate regressions were used to compare perioperative transfusion rates and postoperative outcomes, such as rate of return to the operating room, 30-day readmission, and intensive care unit and hospital length of stay between the 2 treatment groups.

Results:

This study included 975 patients who received antifibrinolytics and 223 patients who did not. Patients who received these agents tended to have more levels fused, osteotomies performed, and longer operative times. After controlling for these variances, there were no statistical differences in rate and volume of transfusion, rate of return to the operating room, 30-day readmission, 30-day postoperative complications, or intensive care unit or hospital length of stay between the 2 treatment groups.

Conclusions:

This study did not demonstrate transfusion reduction in the group that received antifibrinolytics. This finding may be, in part, secondary to nonoptimized or nonstandardized protocols for antifibrinolytic use in pediatric deformity surgery or the inability to adequately control for selection bias, as those with greater surgical invasiveness may be more likely to receive antifibrinolytics. Nonetheless, using antifibrinolytics in this population appears safe and not associated with increased perioperative complications.

Level of Evidence:

Level III.
Differential Analysis of the Spinal Cord Shift After Laminoplasty With Upper Extension to the C2 Segment and Conventional Surgery of the C3–C7 Segments
Authors: Wang Yongfeng , Yuan Jie , Lu Xiangdong , Zhao Yibo , Wang Shaowei , Zhao Bin
Published: June 2019

Study Design:

A retrospective controlled study.

Objective:

To clarify the differences of spinal cord shift between laminoplasty with extension to the C2 segment and conventional surgery of the C3–C7 segments.

Summary of Background Data:

For patients of spinal cord compression at C2/C3 or C2, it is difficult to achieve decompression involving only the C3–C7 segments. Therefore, a laminoplasty with upper extension to C2 is needed. Nevertheless, there is not yet a definitive conclusion regarding whether laminoplasty with extension to C2 can achieve a better spinal cord shift than an extension of the C3–C7 segments.

Materials and Methods:

Preoperative and final follow-up Japanese Orthopedic Association scores were recorded. MRI T2 patient images before and after surgery were used for data collection. The anterior subarachnoid spaces, spinal cord diameters, posterior subarachnoid spaces, and dural sac diameters were measured. The distance of spinal cord shift in a single plane was represented by the differences in the sum of the anterior subarachnoid spaces and the spinal cord diameters before and after surgery. The overall distances and distances of each segment backward were compared between the C2–C7 group and the C3–C7 group. All planes were also classified as segments with compression or noncompression, and the differences in backward shift were compared.

Results:

There were no significant differences in Japanese Orthopedic Association score between the C2–C7 and C3–C7 groups at final follow-up and no significant differences in the overall backward shift between the 2 groups. The spinal cord shift of C1, C2, and C2/C3 segments and the segment of the largest shift distance were significantly different between the 2 groups; the spinal cord shift of the segments under compression was larger than that of noncompression.

Conclusions:

Surgery with upper extension to the C2 segment did not increase the overall spinal cord shift; instead, a better effect was achieved by the effective decompression of local compressed segments, thus obtaining an effective expansion and shift of the spinal cord.

Levels of Evidence:

Level II.
Sex Differences on Postoperative Pain and Disability Following Minimally Invasive Lumbar Discectomy
Authors: Patel Dil V. , Yoo Joon S. , Karmarkar Sailee S. , Lamoutte Eric H. , Singh Kern
Published: June 2019

Study Design:

Retrospective cohort.

Objective:

To determine if sex is associated with differences in postoperative pain scores, narcotic consumption, and long-term improvements in pain and disability following minimally invasive lumbar discectomy (MIS LD).

Summary of Background Data:

There exists a question as to what extent sex influences surgical and clinical outcomes following MIS LD.

Methods:

Patients undergoing primary, single-level MIS LD were retrospectively reviewed and stratified on the basis of sex. Immediate postoperative Visual Analog Scale (VAS) pain scores and narcotic consumption were collected. Patient-reported outcomes, including Oswestry Disability Index (ODI), 12-Item Short-Form- (SF-12) Physical Component Score, and VAS back and leg pain, were collected preoperatively and at 6-week, 3-month, 6-month, and 12-month follow-up. Sex differences were tested for an association between immediate postoperative pain, narcotics utilization, and long-term improvements in patient-reported outcomes using linear regression.

Results:

A total of 188 patients were included and 62.8% were male individuals. At the time of surgery, female individuals were older than male individuals (P=0.045). There were no observed differences in other demographic or perioperative characteristics between cohorts. Female individuals had similar inpatient VAS pain scores and narcotic consumption compared with male individuals. Female individuals had a higher ODI score than male individuals preoperatively, however, both cohorts had similar improvements in ODI at all postoperative time points. Both sexes had similar VAS back and leg pain and SF-12 PCS scores preoperatively and at all postoperative time points.

Conclusions:

Our study demonstrated that sex does not affect immediate postoperative pain, narcotic consumption, and long-term recovery following MIS LD. Female individuals demonstrated similar preoperative back and pain scores compared with male individuals but reported greater disability before surgery. However, both sexes experienced similar improvements in pain and disability at all follow-up time points through 12 months. The results of this study may enable providers to better counsel patients regarding the expected improvement in pain and disability.
Circulating Histones Are Major Mediators of Multiple Organ Dysfunction Syndrome in Acute Critical Illnesses
Authors: Cheng Zhenxing , Abrams Simon T. , Alhamdi Yasir , Toh Julien , Yu Weiping , Wang Guozheng , Toh Cheng-Hock
Published: June 2019

Objectives:

Multiple organ dysfunction syndrome is characterized by simultaneous multiple organ failure, which is the leading cause of death in acute critically ill patients. However, what mediates multiple organ dysfunction syndrome is not fully understood. The discovery of toxic effects by extracellular histones on different individual organs strongly suggests their involvement in multiple organ dysfunction syndrome. In this study, we investigate whether circulating histones are major mediators of multiple organ dysfunction syndrome in acute critical illnesses.

Design:

Combination of retrospective clinical studies and animal models with intervention.

Setting:

ICU in a tertiary hospital and research laboratories.

Patients:

Four hundred and twenty ICU patients, including sepsis (140), severe trauma (63), severe pancreatitis (89), and other admission diagnoses (128).

Laboratory Investigation:

Cells from major organs are treated with calf thymus histones or histone-containing sera. Animal models for sepsis, trauma, and acute pancreatitis are treated with antihistone reagents.

Intervention:

Antihistone reagents in in vitro, ex vivo, and animal models.

Measurement and Main Results:

Retrospective analysis of a prospectively recruited ICU cohort demonstrated a strong correlation between circulating histones and organ injury markers and Sequential Organ Failure Assessment scores. Ex vivo experiments showed that patient sera containing high histone levels were toxic to cultured cells from different origins, suggesting their universal toxicity to multiple organs. Animal models of sepsis, trauma, and pancreatitis further demonstrated a temporal correlation between histone levels and disease severity and multiple organ injury. Importantly, antihistone reagents, that is, antihistone single-chain variable fragment and nonanticoagulant heparin, could dramatically reduce multiple organ injury, particularly of the heart and lungs, and improve survival in mouse models.

Conclusions:

High levels of circulating histones are major mediators of multiple organ dysfunction syndrome. Our results indicate that monitoring upon ICU admission could inform on disease severity and developing antihistone therapy holds great potential of reducing multiple organ dysfunction syndrome and improving survival of critically ill patients.
A Progressive Early Mobilization Program Is Significantly Associated With Clinical and Economic Improvement: A Single-Center Quality Comparison Study
Authors: Liu Keibun , Ogura Takayuki , Takahashi Kunihiko , Nakamura Mitsunobu , Ohtake Hiroaki , Fujiduka Kenji , Abe Emi , Oosaki Hitoshi , Miyazaki Dai , Suzuki Hiroyuki , Nishikimi Mitsuaki , Komatsu Mamoru , Lefor Alan Kawarai , Mato Takashi
Published: June 2019

Objectives:

To determine whether a progressive early mobilization protocol improves patient outcomes, including in-hospital mortality and total hospital costs.

Design:

Retrospective preintervention and postintervention quality comparison study.

Settings:

Single tertiary community hospital with a 12-bed closed-mixed ICU.

Patients:

All consecutive patients 18 years old or older were eligible. Patients who met exclusion criteria or were discharged from the ICU within 48 hours were excluded. Patients from January 2014 to May 2015 were defined as the preintervention group (group A) and from June 2015 to December 2016 was the postintervention group (group B).

Intervention:

Maebashi early mobilization protocol.

Measurements and Main Results:

Group A included 204 patients and group B included 187 patients. Baseline characteristics evaluated include age, severity, mechanical ventilation, and extracorporeal membrane oxygenation, and in group B additional comorbidities and use of steroids. Hospital mortality was reduced in group B (adjusted hazard ratio, 0.25; 95% CI, 0.13–0.49; p < 0.01). This early mobilization protocol is significantly associated with decreased mortality, even after adjusting for baseline characteristics such as sedation. Total hospital costs decreased from $29,220 to $22,706. The decrease occurred soon after initiating the intervention and this effect was sustained. The estimated effect was $–5,167 per patient, a 27% reduction. Reductions in ICU and hospital lengths of stay, time on mechanical ventilation, and improvement in physical function at hospital discharge were also seen. The change in Sequential Organ Failure Assessment score and Sequential Organ Failure Assessment score at ICU discharge were significantly reduced after the intervention, despite a similar Sequential Organ Failure Assessment score at admission and at maximum.

Conclusions:

In-hospital mortality and total hospital costs are reduced after the introduction of a progressive early mobilization program, which is significantly associated with decreased mortality. Cost savings were realized early after the intervention and sustained. Further prospective studies to investigate causality are warranted.