bluuebunny/crossref_metadata_2025 huggingface dataset:
A Validation Study for the Automated Analysis of Corticosteroids in Drugs
Authors: Brower James F
Published: February 2020

A validation study for the analysis of seven corticosteroids in tablets, using an automated blue tetrazolium reaction, has been completed. The method is sensitive and applicable to concentrations normally found in dosage forms and does not require extensive sample preparation. Standard deviations for betamethasone, cortisone acetate, dexamethasone, hydrocortisone, methyl prednisolone, prednisolone, and prednisone by the automated procedure are reported, and the assay results were compared to those by the USP or NF method. The interference of common tablet excipients on the automated method was also determined.
Collaborative Study of an Ion Exchange Method for Ephedrine in Ephedrine Sulfate Sirup NF
Authors: Smith Donald J
Published: February 2020

An ion exchange procedure for Ephedrine Sulfate Sirup NF, based on the ability of ephedrine to be retained on a polystyrene sulfonate cation exchange resin column, was studied collaboratively by eight laboratories. The compound is held on the column by a positive charge located in the cationic center of the molecule, it is then eluted with hydrochloric acid, and its ultraviolet absorption is measured. The addition of 57.88 mg ephedrine sulfate to Ephedrine Sulfate Sirup NF resulted in recoveries of 58.39 and 57.72 mg, or 101 and 100%, respectively. Recoveries for collaborative samples, each containing 19.22 and 19.33 mg/5 ml, were 99.8 ± 1.83 and 101 ± 4.09%, respectively.
GLC Determination of DDVP Extracted or Vacuum-Trapped from PVC Resin Formulations
Authors: St Clair Akos D , Lamberton J G , Claeys R R , Goulding R L
Published: February 2020

A vacuum trapping apparatus was developed for the collection of volatiles and for the determination of rates of volatilization of DDVP from Vapona-PVC resin formulations. More than 99% of the total volatiles was collected by this apparatus. To determine the total content of DDVP in the resin four extracting solvents were tested. Acetone was the most effective solvent. An improved GLC procedure was developed for the quantitation of DDVP. Several liquid phases were compared and optimum chromatographic parameters were examined. Tailing peaks were obtained with DC-11 and DC-11 + Epon 1001. Carbowax 20M gave symmetrical peaks, but optimum column efficiency was obtained on a 7% neopentyl glycol adipate column. The relative standard deviation for the analysis of DDVP by GLC was ±1.8%.
Ultraviolet Determination of Strychnine in Commercial Bait Formulations
Authors: Wapensky Lawrence A
Published: February 2020

A UV method of analysis of strychnine suitable for a commercial bait formulation has been devised. The strychnine is extracted in 0.5% (v/v) H2SO4 and the resulting extract is cleaned up. Strychnine is determined by the difference in absorbance at 254 and 287 mµ. The results reported by this approach correlate well with those obtained by a gravimetric determination of strychnine as the strychnine picrate.
Interferences in the Polyvinyl Alcohol-Borate-Iodine Complex
Authors: Monte-Bovi Anthony J
Published: February 2020

The blue complex formed when solutions of iodine and certain grades of polyvinyl alcohol react with borates under specified conditions has been suggested as a qualitative test for ionic boron. This study attempted to determine the effect of other substances on the formation of the blue complex. Many interferences were found. Procedures are modified to circumvent the presence of such interfering substances.
Neutron Activation Analysis of Nitrogen in Feedstuffs
Authors: Doty W H , Wood D E , Schneider E L
Published: February 2020

The application of neutron activation analysis to the determination of nitrogen in various feeds and feedstuffs has been investigated. Samples were bombarded with fast neutrons to induce the 14N(n, 2n)13N reaction. 13N is a positron emitter with a 10 min half-life. The positrons annihilate in or near the sample to produce 0.51 MeV gamma rays, which are then counted in a detector system. Phosphorus and silicon interfere and are compensated for in the technique. A total of 419 individual runs were made on 53 samples covering 16 different types of materials. Total analysis time was 15 min per sample with a production rate of 12 samples per hr. The coefficient of variation of runs by the automated method typically ranged from 0.90 to 1.73 on the different sample groups. A good correlation between protein determined by the Kjeldahl technique and that determined by the automated method was demonstrated.
Determination of Dimers and Polymers in Heated Fats and Oils by Sublimation
Authors: Huang Anita , Firestone David
Published: February 2020

A sublimation procedure is described for separating dimers and polymers from oxidized or polymerized fats and oils. Under the described conditions, involving sublimation at 90°C and 0.02–0.05 mm Hg pressure, common fatty acid methyl esters standards yielded 99–2100% sublimate, methyl esters of commercial vegetable oils yielded 97.4-99.2% sublimate, heated cottonseed oils yielded 64–83% sublimate, a thermal dimer acid yielded 1.0% sublimate, and laboratory-prepared oxidative dimers and polymers yielded 7.5% sublimate. A comparison of the sublimation procedure with urea adduction gave good correlations with thermally oxidized oil samples; however, with fresh vegetable oil or with samples consisting of predominantly thermal or oxidative dimers, sublimation gave more accurate results than urea adduction.
Detection of Toxicity of Aflatoxins, Sterigmatocystin, and Other Fungal Toxins by Lethal Action on Zebra Fish Larvae
Authors: Abedi Z H , Scott P M
Published: February 2020

The effects of 13 fungal toxins (and one derivative) on the larvae of zebra fish, Brachydanio rerio (Hamilton-Buchanan), were investigated. The most toxic were sterigmatocystin, gliotoxin, and aflatoxin B1, which were lethal at concentrations of less than 1 µg/ml. Aflatoxins B2, G1, and G2, stemphone, diacetoxyscirpenol, ochratoxin A, aspertoxin, and patulin also showed toxicity to the larvae, while aflatoxin B1 hemiacetal, penicillic acid, and griseofulvin were non-toxic at the levels tested. Specific morphological effects were noted with sterigmatocystin, aflatoxins, and stemphone. The usefulness of zebra fish larvae as bioassay test organisms for fungal toxins is discussed.
Determination of Alcohol-Insoluble Solids in Frozen Peas
Authors: Winter F H
Published: February 2020

The frozen contents of the package are thawed in a plastic bag and then transferred to a mechanical blender. A portion of the blended sample is refluxed with 95% denatured alcohol, weighed on a filter in a Büchner funnel, and washed with 80% denatured alcohol. The filter is then dried 2 hr and weighed. The method was applied to 18 samples of frozen peas with over 100 replications. The mean standard deviation for six collaborators who replicated two samples five times each was ±0.30.
Differentiation of Geographic Origin of Spices. II. Oregano by Gas Chromatography and Thin Layer Chromatography
Authors: Stahl William H Stahl , Skarzynski Jean N , Voelker William A
Published: February 2020

Both a gas chromatographic and a thin layer chromatographic procedure have been devised to differentiate the origin of oreganos. The gas chromatographic procedure utilizes the observation that the ratio of the concentration of carvacrol to thymol in Greek oregano is approximately 7:1, whereas in Mexican oregano it is 1:1. The decision can be reinforced by a fluorescence thin layer chromatographic technique, using a hexane-ethyl acetate-tetrahydrofuran mixture as the developing solvent. A two-dimensional TLC, using acetone-ethermethylene chloride for the second development, affords a clean-cut separation of all spots and is particularly useful in the diagnosis of mixtures.
Cyclodiene Chemistry. III. Derivative Formation for the Identification of Heptachlor, Heptachlor Epoxide, cis-Chlordane, irans-Chlordane, Dieldrin, and Chromatography
Authors: Chau Alfred S Y , Cochrane W P
Published: February 2020

An improved method, involving potassium tert.-butoxide and tert.-butanol treatment followed by acetylation, is described for the similtaneous confirmation of heptachlor, heptachlor epoxide, and cis- and trans-chlordanes in cleaned-up feed samples. Parent pesticide residues can be identified at levels of 0.01 ppm and above. As a confirmative test for dieldrin, the formation of an acetate and subsequent conversion to a “ketone” by acetic anhydride/ sulfuric acid treatment is used. The concentrated sulfuric acid-catalyzed isomerization of endrin is also reported.
Derivative Formation for the Confirmation of Endosulfan by Gas Chromatography
Authors: Chal A S Y
Published: February 2020

Chemical conversions followed by GLC analysis are described for the confirmation of residues of α- and β-endosulfan in agricultural crops. Both isomers were reduced to the same diol by lithium aluminum hydride in tetrahydrofuran. Subsequent silylation to the disilyl ether can be used for the routine confirmation of both isomers down to a level of 0.02 p pm in a 10 g sample extract. Alternatively, the insecticide or its reduction product can be acetylated. By this procedure, 0.03 ppm or more of the parent insecticide can be identified in a 10 g sample extract.
The Gene Introgression Approach and the Potential Cost of Genes that Confer Strong Phosphine Resistance in Red Flour Beetle (Coleoptera: Tenebrionidae)
Authors: Daglish Gregory J , Jagadeesan Rajeswaran , Nayak Manoj K , McCulloch Graham A , Singarayan Virgine T , Walter Gimme H
Published: February 2020

Resistance in pest insects to the grain fumigant phosphine (PH3) poses a threat to trade and food security. The possible pleiotropic effects of PH3 resistance on development and reproduction were investigated in the red flour beetle, Tribolium castaneum (Herbst), by introgressing two genes known to be major contributors to strong resistance (tc_rph1 and tc_rph2) into a susceptible background. The tc_rph2 allele was the G135S variant, whereas the identity of tc_rph1 allele was unknown but could have been one of the three known variants (L119W, V123F, or S349G). The introgressed resistant strain was 288× more resistant than the susceptible strain, based on mortality after a 20 h fumigation with PH3. Molecular screening confirmed that the introgressed strain was homozygous for the resistance genes, but was otherwise indistinguishable from the susceptible strain based on screening with 12 neutral DNA markers. We found no differences of consequence in developmental time between the susceptible and introgressed resistant strains. Similarly, the number of F1 adults produced by these strains was more or less equal, as was the weight of individual F1 adults. The conclusions remained the same regardless of whether the experiments were conducted on a flour-based medium or wheat. Thus, we found no evidence that being fully strongly PH3 resistant (i.e., homozygous for tc_rph1 and tc_rph2) has major consequences in terms of development or reproduction in T. castaneum.
Metabolic Regulation of Hippocampal Neuroprogenitor Apoptosis After Irradiation
Authors: Li Yu-Qing , Koritzinsky Marianne , Wong C Shun
Published: February 2020

The tumor suppressor p53 is an important regulator of cell fate response after DNA damage. Cell fate response following metabolic stresses has also been linked to p53-dependent pathways. In this study, we asked if 5′-adenosine monophosphate-activated protein kinase (AMPK), the master sensor of cellular energy balance, played a role in p53-dependent apoptosis of neural progenitor cells (NPCs) in the hippocampus after irradiation. Adult mice with targeted disruption of p53 or prkaa2 (gene that encodes AMPKα) in the brain were used to determine the role of p53 and AMPK, respectively, in radiation-induced apoptosis of NPCs in the hippocampus. The p53-dependent apoptosis of NPCs was associated with an increase in phospho-AMPK expression in the dentate gyrus at 8 hours after irradiation. Activation of AMPK was seen in granule neurons and subgranular NPCs. Compared with wildtype mice, apoptosis of NPCs was significantly attenuated in AMPK deficient (nestinCre: prkaa2fl/fl) mice after irradiation. AMPK deficiency did not however alter p53 activation in NPCs after irradiation. We conclude that AMPK may regulate apoptosis of hippocampal NPCs after irradiation. These findings suggest that cellular metabolism may play a role in determining cell fate response such as apoptosis after DNA damage in NPCs.
Mortality and Functional Outcome Predictors in Combat-Related Penetrating Brain Injury Treatment in a Specialty Civilian Medical Facility
Authors: Sirko Andrii , Pilipenko Grigoriy , Romanukha Dmytro , Skrypnik Alexander
Published: February 2020

Introduction

The combined use of new types of weapons and new types of personal protective equipment has led to changes in the occurrence, nature, and severity of penetrating brain wounds. The availability of modern equipment, methods of treatment, and trained medical personnel in a civilian hospital, as well as advanced specialty medical care, has improved treatment outcomes. There have been a limited number of publications regarding analysis and predictors of treatment outcomes in patients with combat-related penetrating brain injury in contemporary armed conflicts. The purpose of this study was to analyze the results of surgical treatment of patients with penetrating brain injury and to identify significant outcome predictors in these patients.

Materials and Methods

This was a prospective analysis of penetrating brain injury in patients who were admitted to Mechnikov Dnipropetrovsk Regional Clinical Hospital, Ukraine, from May 9, 2014, to December 31, 2017. All wounds were sustained during local armed conflict in Eastern Ukraine. The primary outcomes of interest were mortality rate at 1 month and Glasgow Outcome Scale score at 12 months after the injury.

Results

In total, 184 patients were identified with combat-related brain injury; of those, 121 patients with penetrating brain injury were included in our study. All patients were male soldiers with a mean age of 34.1 years (standard deviation [SD], 9.1 years). Mean admission Glasgow Coma Scale score was 10 (SD, 4), and mean admission Injury Severity Score was 27.7 (SD, 7.6). Mortality within 1 month was 20.7%, and intracranial purulent-septic complications were diagnosed in 11.6% of the patients. Overall, 65.3% of the patients had favorable outcome (good recovery or moderate disability) based on Glasgow Outcome Scale score at 12 months after the injury. The following were predictors of mortality or poor functional outcome at 1 year after the injury: low Glasgow Coma Scale score on admission, gunshot wound to the head, dural venous sinuses wound, presence of intracerebral hematomas, intraventricular and subarachnoid hemorrhage accompanied by lateral or axial dislocation, and presence of intracranial purulent-septic complications.

Conclusions

Generally, combat-related penetrating brain injuries had satisfactory treatment outcomes. Treatment outcomes in this study were comparable to those previously reported by other authors in military populations and significantly better than outcomes of peacetime penetrating brain injury treatment.
An intergenic “safe haven” region in Aspergillus fumigatus
Authors: Pham Tuyetnhu , Xie Xiaofeng , Lin Xiaorong
Published: February 2020

Aspergillus fumigatus is the most common opportunistic human fungal pathogen responsible for invasive aspergillosis. Gene manipulation is critical for the investigation of A. fumigatus biology and pathogenesis at the molecular level, and it often requires integration of the introduced DNA into the fungal genome. Here we have searched and identified two potential “safe haven” regions, SH1 and SH2, based on A. fumigatus genome annotation and transcriptome data. When a DNA fragment carrying a fluorescent protein gene mNeonGreen (mNG) and a drug selection marker was inserted into SH1 or SH2, the expression of mNeonGreen was easily detected, indicating that SH1 and SH2 are not surpressive genetic regions. We found that insertion of this DNA fragment into SH1 did not cause any significant changes in the expression of neighboring genes. Insertion of this DNA into either SH1 or SH2 did not significantly alter any of the phenotypes that we analyzed comparing to the wild type control. By comparison, transformants with random ectopic integration of the same DNA fragment showed a wider range of variation in mNeonGreen expression and in virulence in an insect infection model. Having identified predetermined “safe-haven” regions in A. fumigatus could therefore help reduce experimental variations and increase reproducibility, as it has been for the C. neoformans field.
Online Bayesian Phylodynamic Inference in BEAST with Application to Epidemic Reconstruction
Authors: Gill Mandev S , Lemey Philippe , Suchard Marc A , Rambaut Andrew , Baele Guy
Published: February 2020

Reconstructing pathogen dynamics from genetic data as they become available during an outbreak or epidemic represents an important statistical scenario in which observations arrive sequentially in time and one is interested in performing inference in an “online” fashion. Widely used Bayesian phylogenetic inference packages are not set up for this purpose, generally requiring one to recompute trees and evolutionary model parameters de novo when new data arrive. To accommodate increasing data flow in a Bayesian phylogenetic framework, we introduce a methodology to efficiently update the posterior distribution with newly available genetic data. Our procedure is implemented in the BEAST 1.10 software package, and relies on a distance-based measure to insert new taxa into the current estimate of the phylogeny and imputes plausible values for new model parameters to accommodate growing dimensionality. This augmentation creates informed starting values and re-uses optimally tuned transition kernels for posterior exploration of growing data sets, reducing the time necessary to converge to target posterior distributions. We apply our framework to data from the recent West African Ebola virus epidemic and demonstrate a considerable reduction in time required to obtain posterior estimates at different time points of the outbreak. Beyond epidemic monitoring, this framework easily finds other applications within the phylogenetics community, where changes in the data—in terms of alignment changes, sequence addition or removal—present common scenarios that can benefit from online inference.
The Volta: A Galant Gesture of Culmination
Authors: Mitchell Nathaniel
Published: February 2020

This article presents an overview of a new pre-cadential schema in the galant style: the Volta. The Volta is a two-part schema featuring a prominent chromatic reversal: stage one charges up the dominant with a ♯4^–5^ melodic string, while stage two releases to the tonic using a ♮4^–3^ string. The schema sheds light on many aspects of galant music-making: its variants illustrate how central features of a schematic prototype motivate or constrain plausible manipulations, its pre-cadential function reveals the intimate communion between surface schemas and the harmonic patterns inscribed within the style’s formal scripts, and, finally, its use as a climactic gesture in opera seria calls attention to the semantic possibilities of schemas beyond their role in defining musical topics. These and other aspects of the Volta are illustrated using representative excerpts from eighteenth-century masters like Leonardo Vinci, Giovanni Battista Pergolesi, Johann Adolf Hasse, Baldassare Galuppi, Joseph Haydn, and Wolfgang Amadeus Mozart.
Legal, Moral and Political Determinants within the Social Determinants of Health: Approaching Transdisciplinary Challenges through Intradisciplinary Reflection
Authors: Coggon John
Published: February 2020

This article provides a critical analysis of ‘the legal’ in the legal determinants of health, with reference to the Lancet–O’Neill report on that topic. The analysis shows how law is framed as a fluid and porous concept, with legal measures and instruments being conceived as sociopolitical phenomena. I argue that the way that laws are grounded practically as part of a broader concept of politics and evaluated normatively for their instrumental value has important implications for the study of law itself. This, in turn, has implications for how we approach the transdisciplinary ambitions that form a key part of the report’s recommendations to enhance law’s capacity to promote better, more equitable population health at local, national, international and global levels.
Population Diversity and Structure of Podosphaera macularis in the Pacific Northwestern United States and Other Populations
Authors: Gent David H. , Claassen Briana J. , Gadoury David M. , Grünwald Niklaus J. , Knaus Brian J. , Radišek Sebastjan , Weldon William , Wiseman Michele S. , Wolfenbarger Sierra N.
Published: February 2020

Powdery mildew, caused by Podosphaera macularis, is one of the most important diseases of hop. The disease was first reported in the Pacific Northwestern United States, the primary hop-growing region in this country, in the mid-1990s. More recently, the disease has reemerged in newly planted hopyards of the eastern United States, as hop production has expanded to meet demands of local craft brewers. The spread of strains virulent on previously resistant cultivars, the paucity of available fungicides, and the potential introduction of the MAT1-2 mating type to the western United States, all threaten sustainability of hop production. We sequenced the transcriptome of 104 isolates of P. macularis collected throughout the western United States, eastern United States, and Europe to quantify genetic diversity of pathogen populations and elucidate the possible origins of pathogen populations in the western United States. Discriminant analysis of principal components grouped isolates within three to five geographic populations, dependent on stringency of grouping criteria. Isolates from the western United States were phenotyped and categorized into one of three pathogenic races based on disease symptoms generated on differential cultivars. Western U.S. populations were clonal, irrespective of pathogenic race, and grouped with isolates originating from Europe. Isolates originating from wild hop plants in the eastern United States were genetically differentiated from all other populations, whereas isolates from cultivated hop plants in the eastern United States mostly grouped with isolates originating from the west, consistent with origins from nursery sources. Mating types of isolates originating from cultivated western and eastern U.S. hop plants were entirely MAT1-1. In contrast, a 1:1 ratio of MAT1-1 and MAT1-2 was observed with isolates sampled from wild plants or Europe. Within the western United States a set of highly differentiated loci were identified in P. macularis isolates associated with virulence to the powdery mildew R-gene R6. The weight of genetic and phenotypic evidence suggests a European origin of the P. macularis populations in the western United States, followed by spread of the pathogen from the western United States to re-emergent production regions in the eastern United States. Furthermore, R6 compatibility appears to have been selected from an extant isolate within the western United States. Greater emphasis on sanitation measures during propagation and quarantine policies should be considered to limit further spread of novel genotypes of the pathogen, both between and within production areas.
Opioid Utilization in Geriatric Patients After Operation for Degenerative Spine Disease
Authors: Nguyen Anthony V. , Ross Evan , Westra Jordan , Huang Nicole , Nguyen Christine Y. , Raji Mukaila , Lall Rishi , Kuo Yong-Fang
Published: February 2020

Background:

Few studies have investigated opioid utilization by geriatric patients after spinal surgery, a population in whom degenerative spine disease (DSD) is highly prevalent. We aimed to quantify rates of chronic, continuous opioid utilization by geriatric patients following spine surgery for DSD-related diagnoses.

Materials and Methods:

Utilizing a national 5% Medicare sample database, we investigated individuals aged above 66 years who underwent spinal surgery for a DSD-related diagnosis between the years of 2008 and 2014. The outcomes of interest were the rate of and risk factors for continuous opioid utilization at 1-year following anterior cervical discectomy and fusion, posterior cervical fusion, 360-degree cervical fusion, lumbar microdiscectomy, lumbar laminectomy, posterior lumbar fusion, anterior lumbar fusion, or 360-degree lumbar fusion for a DSD-related diagnosis.

Results:

Of the 14,583 Medicare enrollees who met study criteria, 6.0% continuously utilized opioids 1-year after spinal surgery. When stratified by preoperative opioid utilization (with the prior year divided into 4 quarters), the rates of continuous utilization at 1-year postsurgery were 0.3% of opioid-naive patients and 23.6% of patients with opioid use in all 4 quarters before surgery. Anxiety, benzodiazepine use within the year before surgery, and Medicaid dual-eligibility were associated with prolonged opioid utilization.

Conclusions:

Of opioid-naive geriatric patients who underwent surgery for DSD, 0.3% developed chronic, continuous opioid use. Preoperative opioid use was the strongest predictor of prolonged utilization, which may represent suboptimal use of nonopioid alternatives, pre-existing opioid use disorders, delayed referral for surgical evaluation, or over-prescription of opioids for noncancer pain.
Improving Microbe Detection and Optimizing Antibiotic Use in Neonatal Sepsis With Multiplex Polymerase Chain Reaction
Authors: Raju Vivek , Pournami Femitha , Nandakumar Anand , Prabhakar Jyothi , Nair PMC , Jain Naveen
Published: February 2020

Background

Polymerase chain reaction (PCR) can overcome the drawbacks of culture in diagnosis of neonatal sepsis. Many reports have shown potential benefit.

Aim

We compared microbe detection rate between 2 groups—when PCR was used along with blood culture (culture + PCR, CP) versus when culture alone was used. We also sought to describe, in CP, the causal organisms and their resistance patterns and to study duration of antibiotic therapy in CP versus culture alone groups.

Methods

We studied a prospective cohort of babies where both culture and PCR could be sent and a retrospective cohort when only culture was used; in those who required antibiotic for suspected health care–associated infection.

Results

When PCR was used along with culture, microbes were detected in 40.3% samples, as against only 24.6% with culture alone. Gram-negative bacilli were the most common organism detected (56.5% of positive samples) followed by Candida species. Resistance was reported in only 3 of the tested gram-negative organisms. Empiric antibiotics were stopped significantly earlier in the cohort where PCR was also used as compared with when culture alone was relied upon (median duration of therapy 3 vs 7 days, respectively).

Conclusions

Polymerase chain reaction improves diagnostic yield in neonatal health care–associated infection and can help decrease duration of antibiotic therapy. Resistance to broad spectrum antibiotics is uncommon.
New method to assess the accuracy of intraocular lens power calculation formulas according to ocular biometric parameters
Authors: Fernández Joaquín , Rodríguez-Vallejo Manuel , Poyales Francisco , Burguera Noemí , Garzón Nuria
Published: February 2020

Purpose:

To develop a new method that makes it easy to detect accuracy deficiencies of any intraocular lens (IOL) power calculation formulas and to test it on 9 different formulas.

Setting:

IOA, Madrid, Spain.

Design:

Retrospective observational case series.

Methods:

This study's first stage included 3519 eyes from 3519 candidates for cataract surgery for which frequency distributions for the following biometric eye parameters were computed: axial length (AL), anterior chamber depth (ACD), lens thickness (LT), white-to-white (WTW), and mean corneal radius (Rm). The resulting data for each parameter were fifth, 25th, 75th and 95th percentiles, which allowed definition of the corresponding normality range. In a second stage, the new graphic-representation method was tested for 9 different formulas in a sample of 70 eyes undergoing cataract surgery with multifocal IOL (mIOL) implantation.

Results:

Normality ranges (defined as the 25th to 75th percentile interval) were 22.84 to 24.42 mm for AL, 2.86 to 3.39 mm for ACD, 4.36 to 4.88 mm for LT, 11.64 to 12.19 mm for WTW, and 7.52 to 7.87 mm for Rm, with lower sizes in women. No significant differences were found among the 9 formulas for percentage of eyes in ±0.50 diopters (D) (P = .82) or ±1.00 D (P = .97). The graphical method showed less accuracy in ±0.50 D for ACDs from 2.46 to 2.85 mm (5th to 25th percentile) for several formulas (P < .05).

Conclusions:

Nine formulas showed nonsignificant differences in the general predictability for a sample of eyes that were candidates to mIOL implantation. Predictability in this sample decreased for short ACDs.
Experimental and analytical quantification of light scattering from vacuoles in intraocular lenses
Authors: Spiezio Vincent , Walker Bennett N. , Calogero Don , Ilev Ilko K.
Published: February 2020

Purpose:

To develop an advanced test methodology for quantification of scattered light from intraocular lenses (IOLs) and to evaluate the correlation between IOL vacuole characteristics and measured scattered light.

Setting:

U.S. Food and Drug Administration, Optical Therapeutics and Medical Nanophotonics Laboratory, Silver Spring, Maryland, USA.

Design:

Experimental and analytical study.

Methods:

Twenty-four IOLs containing vacuoles were evaluated using a digital microscopy approach for identifying and characterizing the vacuoles present. A scanning light scattering profiler (SLSP) was used to evaluate and quantify the amount of scattered light from each IOL and from a 25th control IOL without any vacuoles. A variety of IOLs and vacuoles were also modeled in a Zemax simulation of the SLSP, and the simulated scattered light was modeled.

Results:

The scattered light as measured with SLSP was well correlated with vacuole characteristics, specifically density and size, as measured under the digital microscope for the 24 vacuole-containing IOLs. Additional correlations were found between vacuole sizes, orientations, and the angle at which light was scattered most severely. These correlations were also present in the Zemax model.

Conclusions:

Vacuole optical characteristics can be well correlated with measured scatter, demonstrating an ability to predict scattered light based solely on microscope evaluation. Furthermore, the quantitative amount of scatter predicted with Zemax simulations trended closely with the experimentally measured trends.
The Language of Electricity
Authors: Kivnick Alexandra R. , Limone Brittanya , Jacob Sharon E.
Published: February 2020

Electrical devices are commonly used within the field of dermatologic surgery. With the growing role of nursing providers in the dermatologic setting, it is essential to provide education and training regarding electrical devices and concepts within the nursing community. This installment introduces electricity principles and reviews terminology associated with the electrical devices used in dermatologic procedures.
Nonalcoholic fatty liver disease is associated with intrahepatic cholangiocarcinoma and not with extrahepatic form: definitive evidence from meta-analysis and trial sequential analysis
Authors: Corrao Salvatore , Natoli Giuseppe , Argano Christiano
Published: February 2020

Background

Cholangiocarcinoma is a cancer with poor prognosis. The detection of risk factors is fundamental to identify subjects at higher risk of cholangiocarcinoma. Nonalcoholic fatty liver disease (NAFLD) represents a leading cause of chronic liver disease worldwide. Recent data suggested that NAFLD increases the risk of cholangiocarcinoma development. However, it is necessary to better explain the strength of association between NAFLD and cholangiocarcinoma.

Methods

A systematic research of current case-control, cohort, clinical trial and meta-analysis on the main electronic databases was made. A recent systematic review was recognized. We performed cumulative meta-analyses with sensitivity analysis excluding studies with large sample size and with great clinical heterogeneity, then we checked for further studies. At the final step, three trial sequential analyses were done as well.

Results

NAFLD determines an increased risk of total cholangiocarcinoma and intrahepatic cholangiocarcinoma (iCCA) development: odds ratio (OR) (95% confidence interval [CI]): 1.88 (1.25–2.83), OR (95% CI): 2.19 (1.48–3.25), respectively. On the contrary, NAFLD does not show a significant effect on extrahepatic cholangiocarcinoma (eCCA) (OR (95% CI): 1.48 (0.93–2.36). The trial sequential analyses regarding total cholangiocarcinoma and iCCA showed that z-curve was outside computed alpha boundaries, proving that the positive association was conclusive. The trial sequential analysis about eCCA showed that z-curve was inside computed futile boundaries, proving that negative results were conclusive.

Conclusion

The performance of new sensitive analyses and the respective trial sequential analyses, after withdraw of confounding factors, suggested the existence of definitive association only between NAFLD and iCCA development and not with eCCA.
Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma
Authors: Meier Raphael P.H. , Muller Yannick D. , Dietrich Pierre-Yves , Tille Jean-Christophe , Nikolaev Sergey , Sartori Ambra , Labidi-Galy Intidhar , Ernandez Thomas , Kaur Amandeep , Hirsch Hans H. , McKee Thomas A. , Toso Christian , Villard Jean , Berney Thierry
Published: February 2020

Background.

Metastatic carcinoma of a renal allograft is a rare but life threatening event with a difficult clinical management. Recent reports suggested a potential role of BK polyomavirus (BKPyV) in the development of urologic tract malignancies in kidney transplant recipients.

Methods.

We investigated a kidney-pancreas female recipient with an history of BKPyV nephritis who developed a rapidly progressive and widely metastatic donor-derived renal carcinoma 9 years after transplantation.

Results.

Histology and fluorescence in situ hybridization analysis revealed a donor-derived (XY tumor cells) collecting (Bellini) duct carcinoma. The presence of BKPyV oncogenic large tumor antigen was identified in large amount within the kidney tumor and the bowel metastases. Whole genome sequencing of the tumor confirmed multiple genome BKPyV integrations. The transplanted kidney was removed, immunosuppression was withdrawn, and recombinant interleukin-2 (IL-2) was administered for 3 months, inducing a complete tumor clearance, with no evidence of disease at 6-year follow-up. The immunological profiling during IL-2 therapy revealed the presence of donor-specific T cells and expanded cytokine-producing bright natural killer cells but no donor-specific antibodies. Finally, we found persistently elevated anti-BK virus IgG titers and a specific anti-BKPyV T cell response.

Conclusions.

This investigation showed evidence for the potential oncogenic role of BKPyV in collecting duct carcinoma in renal allografts and demonstrated that immunosuppression withdrawal and IL-2 therapy can lead to an efficient antitumor cellular mediated rejection possibly via 3 distinct mechanisms including (1) host-versus-graft, (2) host-versus-tumor, and (3) anti-BKPyV responses.
Normothermic Ex Vivo Liver Perfusion Prevents Intrahepatic Platelet Sequestration After Liver Transplantation
Authors: Kollmann Dagmar , Linares-Cervantes Ivan , Ganesh Sujani , Rosales Roizar , Hamar Matyas , Goto Toru , Urbanellis Peter , Tessandier Nicolas , Boilard Eric , Bruguera Claudia , Wiebe Aryn , Bartczak Agata , Yip Paul , Adeyi Oyedele , Selzner Markus , Selzner Nazia
Published: February 2020

Background.

The detrimental role of platelets in sinusoidal endothelial cell (SEC) injury during liver transplantation (LT) has been previously addressed after static cold storage (SCS), however, it is currently unknown after normothermic ex vivo liver perfusion (NEVLP).

Methods.

Pig LT was performed with livers from heart-beating donors or donation after circulatory death (DCD) donors subjected to SCS or NEVLP (n = 5/group).

Results.

All pigs except for 1 (DCD-SCS-group) survived 4 days. The heart-beating donor- and DCD-NEVLP-groups showed significantly lower aspartate transaminase-levels compared with the SCS-groups 3 hours post-LT (P = 0.006), on postoperative day (POD) 2 (P = 0.005), POD3 (P = 0.007), and on POD4 (P = 0.012). Post-LT total platelet count recovered faster in the NEVLP than in the SCS-groups at 12 hours (P = 0.023) and 24 hours (P = 0.0038). Intrahepatic sequestration of platelets was significantly higher in the SCS-groups 3 hours postreperfusion and correlated with severity of SEC injury. In both SCS-groups, levels of tumor growth factor-β were higher 3 hours post-LT, on POD1 and on POD3. Moreover, platelet factor 4 levels and platelet-derived extracellular vesicles were increased in the SCS-groups. Hyaluronic acid levels were significantly higher in the SCS-groups, indicating a higher grade of endothelial cell dysfunction. Platelet inhibition achieved by pretreatment with clopidogrel (n = 3) partly reversed the detrimental effects on SEC injury and therefore provided further evidence of the important role of platelets in ischemia/reperfusion injury and SEC injury.

Conclusions.

Normothermic perfusion of liver grafts before transplantation effectively reduced platelet aggregation and SEC injury, which translated into an improved posttransplant organ function.
Exploring modularity in biological networks
Authors: Serban Maria
Published: February 2020

Network theoretical approaches have shaped our understanding of many different kinds of biological modularity. This essay makes the case that to capture these contributions, it is useful to think about the role of network models in exploratory research. The overall point is that it is possible to provide a systematic analysis of the exploratory functions of network models in bioscientific research. Using two examples from molecular and developmental biology, I argue that often the same modelling approach can perform one or more exploratory functions, such as introducing new directions of research, offering a complementary set of concepts, methods and algorithms for individuating important features of natural phenomena, generating proofs of principle demonstrations and potential explanations for phenomena of interest and enlarging the scope of certain research agendas.

This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.
‘Hierarchy’ in the organization of brain networks
Authors: Hilgetag Claus C. , Goulas Alexandros
Published: February 2020

Concepts shape the interpretation of facts. One of the most popular concepts in systems neuroscience is that of ‘hierarchy’. However, this concept has been interpreted in many different ways, which are not well aligned. This observation suggests that the concept is ill defined. Using the example of the organization of the primate visual cortical system, we explore several contexts in which ‘hierarchy’ is currently used in the description of brain networks. We distinguish at least four different uses, specifically, ‘hierarchy’ as a topological sequence of projections, as a gradient of features, as a progression of scales, or as a sorting of laminar projection patterns. We discuss the interpretation and functional implications of the different notions of ‘hierarchy’ in these contexts and suggest that more specific terms than ‘hierarchy’ should be used for a deeper understanding of the different dimensions of the organization of brain networks.

This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.
Hierarchy and levels: analysing networks to study mechanisms in molecular biology
Authors: Bechtel William
Published: February 2020

Network representations are flat while mechanisms are organized into a hierarchy of levels, suggesting that the two are fundamentally opposed. I challenge this opposition by focusing on two aspects of the ways in which large-scale networks constructed from high-throughput data are analysed in systems biology: identifying clusters of nodes that operate as modules or mechanisms and using bio-ontologies such as gene ontology (GO) to annotate nodes with information about where entities appear in cells and the biological functions in which they participate. Of particular importance, GO organizes biological knowledge about cell components and functions hierarchically. I illustrate how this supports mechanistic interpretation of networks with two examples of network studies, one using epistatic interactions among genes to identify mechanisms and their parts and the other using deep learning to predict phenotypes. As illustrated in these examples, when network research draws upon hierarchical information such as provided by GO, the results not only can be interpreted mechanistically but provide new mechanistic knowledge.

This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.
Network architectures supporting learnability
Authors: Zurn Perry , Bassett Danielle S.
Published: February 2020

Human learners acquire complex interconnected networks of relational knowledge. The capacity for such learning naturally depends on two factors: the architecture (or informational structure) of the knowledge network itself and the architecture of the computational unit—the brain—that encodes and processes the information. That is, learning is reliant on integrated network architectures at two levels: the epistemic and the computational, or the conceptual and the neural. Motivated by a wish to understand conventional human knowledge, here, we discuss emerging work assessing network constraints on the learnability of relational knowledge, and theories from statistical physics that instantiate the principles of thermodynamics and information theory to offer an explanatory model for such constraints. We then highlight similarities between those constraints on the learnability of relational networks, at one level, and the physical constraints on the development of interconnected patterns in neural systems, at another level, both leading to hierarchically modular networks. To support our discussion of these similarities, we employ an operational distinction between the modeller (e.g. the human brain), the model (e.g. a single human’s knowledge) and the modelled (e.g. the information present in our experiences). We then turn to a philosophical discussion of whether and how we can extend our observations to a claim regarding explanation and mechanism for knowledge acquisition. What relation between hierarchical networks, at the conceptual and neural levels, best facilitate learning? Are the architectures of optimally learnable networks a topological reflection of the architectures of comparably developed neural networks? Finally, we contribute to a unified approach to hierarchies and levels in biological networks by proposing several epistemological norms for analysing the computational brain and social epistemes, and for developing pedagogical principles conducive to curious thought.

This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.
From inert matter to the global society life as multi-level networks of processes
Authors: Chavalarias David
Published: February 2020

A few billion years have passed since the first life forms appeared. Since then, life has continued to forge complex associations between the different emergent levels of interconnection it forms. The advances of recent decades in molecular chemistry and theoretical biology, which have embraced complex systems approaches, now make it possible to conceptualize the questions of the origins of life and its increasing complexity from three complementary notions of closure: processes closure, autocatalytic closure and constraints closure. Developed in the wake of the second-order cybernetics, this triple closure approach, that relies on graph theory and complex networks science, sketch a paradigm where it is possible to go up the physical levels of organization of matter, from physics to biology and society, without resorting to strong reductionism. The phenomenon of life is conceived as the contingent complexification of the organization of matter, until the emergence of life forms, defined as a network of auto-catalytic process networks, organized in a multi-level manner. This approach of living systems, initiated by Maturana & Varela and Kauffman, inevitably leads to a reflection on the nature of cognition; and in the face of the deep changes that affected humanity as a complex systems, on the nature of cultural evolution. Faced with the major challenges that humanity will have to address in the decades to come, this new paradigm invites us to change our conception of causality by shifting our attention from state change to process change and to abandon a widespread notion of 'local' causality in favour of complex systems thinking. It also highlights the importance of a better understanding of the influence of social networks, recommendation systems and artificial intelligence on our future collective dynamics and social cognition processes.

This article is part of the theme issue ‘Unifying the essential concepts of biological networks: biological insights and philosophical foundations’.