bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a nonhuman primate computational phantom for radiation dosimetry
Authors: Xie Tianwu , Park Jin Seo , Zhuo Weihai , Zaidi Habib
Published: December 2019

Purpose

The nonhuman primate (NHP) is an important animal model for evaluating the response of the human body to radiation exposure owing to similarities between its organ structure, genome, life span, and metabolism. However, there is a lack of radiation dosimetry estimations for NHPs. The aim of this work is to construct a computational phantom of NHPs and estimate absorbed fractions and specific absorbed fractions for internal radiation dosimetry.

Materials and methods

A female rhesus monkey was frozen and sectioned using a cryomacrotome. The transaxial sectioned images were imported into Adobe Photoshop for segmentation of internal organs. A total of 31 organs/tissues were identified and labeled. The segmented voxel phantom was then converted to a boundary representation (BREP) phantom to enable easy alteration of the phantom to mimic monkeys of different stature. The BREP model was then voxelized and imported into the MCNPX Monte Carlo radiation transport code for electron and photon dosimetry calculations. To estimate the appropriateness of using human phantoms as surrogate models for NHPs, absorbed fractions (AFs) and specific absorbed fractions (SAFs) of monoenergetic electrons and photons were calculated and compared with the ICRP reference newborn female phantom and a 1‐yr‐old female phantom.

Results

Considerable differences were observed for both self‐absorbed and cross‐absorbed doses for some organs between the NHP phantom and newborn phantom. For example, the ratios of the self‐absorbed SAF(stomach wall) Monkey to SAF(stomach wall) Newborn ranged from 0.06 at 10 keV to 0.29 at 3 MeV for photons while the corresponding ratios to cross‐absorbed SAF(liver→kidney) Monkey to SAF(liver→kidney) Newborn ranged from 0.78 at 50 keV to 5.78 at 10 keV for photons. Conversely, values of self‐absorbed SAF were much higher (ratios of 2.39–4.19) for the brain and much lower for the uterus (0.51–0.61) in the monkey model compared to the newborn phantom. These dose differences can be attributed to the disparities between organ masses, shapes, and positions between the two phantoms.

Conclusions

The developed NHP model can be exploited for the assessment of radiation dose to NHPs in preclinical radiation dosimetry studies and radiation therapy research.
Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study
Authors: Harvey Philip D. , Nakamura Hiroshi , Miura Sadanori
Published: December 2019

Objective

To report the efficacy and safety of blonanserin in patients with schizophrenia compared with risperidone in a Japanese multicenter, randomized, double‐blind study based on post hoc sensitivity analysis in addition to the previous results reported by Miura and discuss the current approaches for schizophrenia treatment.

Methods

Of 302 patients randomized, 156 received blonanserin (8‐24 mg/d) and 145 received risperidone (2‐6 mg/d) for 8 weeks. Efficacy variables included the Positive and Negative Syndrome Scale (PANSS) total score for the primary outcome, PANSS subscale, Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression‐Improvement (CGI‐I) for secondary outcomes. Safety variables included treatment‐emergent adverse events, Drug Induced Extrapyramidal Symptoms Scale scores, laboratory data, vital signs, electrocardiogram, etc

Results

Blonanserin was not inferior to risperidone in the change in PANSS total score at a non‐inferior margin of −7 (intergroup difference, −0.46; 95% CI, −4.40 to 3.48). Post hoc analyses wholly supported the primary result. No major difference was found in the changes in BPRS scores and the improvement rate on CGI‐I between the drugs. The incidence of adverse events was similar in the two drugs. Blonanserin was associated with a lower risk of prolactin increase, weight gain, and orthostatic hypotension compared with risperidone. However, blonanserin was associated with a higher incidence of akathisia and excitability compared with risperidone. Most of the adverse events were mild to moderate in severity with no specific events of predominant high severity in the both drugs.

Conclusions

Blonanserin exerted the similar efficacy to risperidone in both positive and negative symptoms in schizophrenia with a lower risk of prolactin increase, weight gain, and orthostatic hypotension compared with risperidone. Blonanserin will serve as a favorable treatment option for schizophrenia in daily clinical practice.
Saathi Sanitary Pads: Eco‐friendly pads which will make you go bananas!
Authors: Tudu Preshita Neha
Published: December 2019

Undoubtedly, menstrual pads have made menstruation hygienic and comfortable. However, these commercial disposable sanitary pads have a devastating effect on the environment and are eco disaster. This case discusses about an initiative taken by an Ahmedabad‐based social enterprise and manufacturing company Saathi and founded by three Massachusetts Institute of Technology graduates ‐‐ Amrita Saigal, Grace Kane and Kristin Kagetsu. Their eco‐friendly, biodegradable sanitary pad is an alternative to non‐biodegradable commercial pads which when discarded ends up in sewage, landfills, fields and water bodies posing threat to environment. Moreover, this pad is also an alternative to commercial pads which are made of plastic, cellulose gel, laded with chemical, bleach and fragrance which leads to serious health issues including cervical cancer, urinary tract infection, infertility and birth defect. The present case of Saathi tries to surface out the relationship between sustainability and marketing by focusing on the concept of sustainability marketing. The case discusses the marketing mix strategy used by Saathi. In a country where menstruation is still a social taboo, the case also talks about the challenges faced by Saathi related to price, the environmental awareness and lack of knowledge about menstruation and ill effects of using commercial pads on women health and whether it should consider expansion of its business and enter into the B2C market in India.
In defence of the osteoma: The relevance of benign tumours in bioarchaeology and palaeo‐oncology
Authors: Siek Thomas
Published: December 2019

Currently, research focus in palaeo‐oncology is dominated by malignant neoplasms, and this focus has led to an academic apathy towards benign tumours. The lack of interest in benign tumours is mainly due to the notion that they are commonplace occurrences with little clinical value. As a result, knowledge and understanding of benign tumours are lacking, and this has become a hindrance to the overall understanding of neoplastic disease in bioarchaeological contexts. It is the goal of this commentary to highlight the relevance of benign tumours and to encourage future research in this neglected area of palaeo‐oncology.
Association of Hepatic Global DNA Methylation and Serum One‐Carbon Metabolites with Histological Severity in Patients with NAFLD
Authors: Lai Zhiwei , Chen Junliang , Ding Chenghe , Wong Kwanshu , Chen Xingyi , Pu Liuzhen , Huang Qiangwei , Chen Xiaolin , Cheng Zijian , Liu Yan , Tan Xuying , Zhu Huilian , Wang Lijun
Published: December 2019

Objective

Clinical relevance of global DNA methylation and one‐carbon metabolite levels with histological severity remains uncertain in patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to evaluate hepatic global DNA methylation and serum one‐carbon metabolite concentrations in patients with NAFLD and the possible associations of these parameters with liver histology.

Methods

Liver biopsies from 18 control participants and 47 patients with NAFLD were evaluated.

Results

The hepatic global DNA methylation level was significantly lower in the NAFLD group than in the control group among participants with overweight. Participants with moderate inflammation and mild fibrosis had significantly lower levels of global DNA methylation than those without these characteristics. Participants with borderline nonalcoholic steatohepatitis had significantly lower global DNA methylation levels than controls. The hepatic global DNA methylation level tended to decrease with the increasing hepatic inflammation grade and disease progression. The NAFLD group had a significantly higher serum homocysteine concentration than the control group among participants with overweight. This level tended to increase with increasing hepatic steatosis grade and disease progression.

Conclusions

Patients with NAFLD exhibited lower hepatic levels of global DNA methylation and elevated serum homocysteine concentrations, which are associated with the histological severity of NAFLD.
Constructing sustained‐release herbicide formulations based on poly‐3‐hydroxybutyrate and natural materials as a degradable matrix
Authors: Kiselev Evgeniy G , Boyandin Anatoly N , Zhila Natalia O , Prudnikova Svetlana V , Shumilova Anna A , Baranovskiy Sergey V , Shishatskaya Ekaterina I , Thomas Sabu , Volova Tatiana G
Published: December 2019

BACKGROUND

The purpose of the present study was to develop ecofriendly herbicide formulations. Its main aim was to develop and investigate slow‐release formulations of herbicides (metribuzin, tribenuron‐methyl, and fenoxaprop‐P‐ethyl) of different structure, solubility, and specificity, which were loaded into a degradable matrix of poly‐3‐hydroxybutyrate (P(3HB)) blended with available natural materials (peat, clay, and wood flour).

RESULTS

Differences in the structure and physicochemical properties of the formulations were studied depending on the type of the matrix. Herbicide release and accumulation in soil were associated with the solubility of the herbicide. Fourier‐transform infrared spectroscopy showed that no chemical bonds were formed between the components in the experimental formulations. Degradation of the formulations in agro‐transformed soil in laboratory conditions was chiefly influenced by the shape of the specimens (granules or pellets) while the effect of the type of filler (peat, clay, or wood flour) was insignificant. The use of granules enabled more rapid accumulation of the herbicides in soil: their peak concentrations were reached after 3 weeks of incubation while the concentrations of the herbicides released from the pellets were the highest after 5–7 weeks. Loading of the herbicides into the polymer matrix composed of the slowly degraded P(3HB) and natural materials enabled both sustained function of the formulations in soil (lasting between 1.5 and ≥3 months) and stable activity of the otherwise rapidly inactivated herbicides such as tribenuron‐methyl and fenoxaprop‐P‐ethyl.

CONCLUSION

The experimental herbicide formulations enabled slow release of the active ingredients to soil. © 2019 Society of Chemical Industry
An ideal solution? Optimising pretreatment methods for artificially mummified ancient Egyptian tissues
Authors: Cockitt Jenefer , Lamb Angela , Metcalfe Ryan
Published: December 2019

Rationale

Although the analysis of skeletal remains dominates the study of ancient dietary stable isotopes, mummified bodies also allow short‐term diet to be studied through the analysis of soft tissues. The application of resins, waxes and oils during mummification can affect the results obtained. This study assesses a range of methods for removing such substances from mummified tissue.

Methods

An experimental mummification model following ancient Egyptian methods was created using a modern pig leg. Sub‐samples of skin, muscle and bone were removed and coated with a range of substances used in Egyptian mummification. Four methods were used to clean these samples before the measurement of the carbon and nitrogen stable isotope ratios of their gelatinised collagen content using a ThermoFinnigan Flash Elemental analyser coupled to a DeltaPlus XL isotope ratio mass spectrometer via a ConFlo III interface.

Results

The results showed that embalming materials can significantly affect dietary stable isotope ratios, and that these substances are most effectively removed using a mixture of polar and non‐polar solvents. Results indicate that bone samples demineralised with HCl and skin samples produce more accurate results than bone samples demineralised with EDTA or muscle samples.

Conclusions

The choice of tissue and the preparation methods used can have a significant effect on the accuracy of stable isotope data obtained from mummified tissue, particularly when embalming materials are also present. A mixture of solvents appears to be a more effective cleaning agent than a single solvent. Demineralisation with HCl is preferable for well‐preserved bone, as used in this study, but whether this is the case for more fragile, less well‐preserved bone requires further study. Skin samples produce more consistent data than muscle, but visually distinguishing between these tissues is not simple on ancient mummies.
The coupling characteristics of population and residential land in rural areas of China and its implications for sustainable land use
Authors: Cai Enxiang , Chen Weiqiang , Wei Hejie , Li Jiwei , Wang Hua , Guo Yulong , Feng Xinwei
Published: December 2019

Understanding the changes and coupling characteristics between rural population (RP) and rural residential land (RRL) provides a theoretical basis for sustainable rural land use. Based on the index of human–land coupling development, this study analyzed the spatial–temporal characteristics and coupling types of RRL and RP on the levels of China's national and prefectural cities by using the data of official land use survey and demographic statistics from 2009 to 2016. Results showed that (a) China's RP is declining at an average annual rate of 2.07%, and the RP in most cities decrease from −3.33% to −1.20%. (b) The area of RRL in China constantly increased at an average annual rate of 0.56% and that of most cities has also maintained growth, with only 11.76% of cities that declined. (c) The per capita RRL in China increased from 267.96 m2 in 2009 to 325.58 m2 in 2016. The relationship between the RRL and RP in China was uncoordinated with a coupling type of G (rapid decline in RP and increase in RRL). The coupling types of most cities were also the uncoordinated type of G, and only less than 10% of cities had a coordinated type (Types B, C, D, and E). The results indicated that the coupling relationship between RP and RRL in China is decoupled and has obvious spatial heterogeneity, which could provide scientific support for optimizing land resources and coordinating human–land relationship in China's rural areas.
Assessing method agreement for paired repeated binary measurements administered by multiple raters
Authors: Wang Wei , Lin Nan , Oberhaus Jordan D. , Avidan Michael S.
Published: December 2019

Method comparison studies are essential for development in medical and clinical fields. These studies often compare a cheaper, faster, or less invasive measuring method with a widely used one to see if they have sufficient agreement for interchangeable use. Moreover, unlike simply reading measurements from devices, eg, reading body temperature from a thermometer, the response measurement in many clinical and medical assessments is impacted not only by the measuring device but also by the rater. For example, widespread inconsistencies are commonly observed among raters in psychological or cognitive assessment studies due to different characteristics such as rater training and experience, especially in large‐scale assessment studies when many raters are employed. This paper proposes a model‐based approach to assess agreement of two measuring methods for paired repeated binary measurements under the scenario where the agreement between two measuring methods and the agreement among raters are required to be studied simultaneously. Based upon the generalized linear mixed models (GLMMs), the decision on the adequacy of interchangeable use is made by testing the equality of fixed effects of methods. Approaches for assessing method agreement, such as the Bland‐Altman diagram and Cohen's kappa, are also developed for repeated binary measurements based upon the latent variables in GLMMs. We assess our novel model‐based approach by simulation studies and a real clinical application, in which patients are evaluated repeatedly for delirium with two validated screening methods. Both the simulation studies and the real data analyses demonstrate that our proposed approach can effectively assess method agreement.
Stabilization of Inorganic CsPb0.5Sn0.5I2Br Perovskite Compounds by Antioxidant Tea Polyphenol
Authors: Ban Huaxia , Sun Qiang , Zhang Tao , Li Hao , Shen Yan , Wang Mingkui
Published: December 2019

Implementation of inorganic perovskite compounds and reduction toxicity of lead are important for developing sustainable and renewable photovoltaic power generation. The inorganic Pb/Sn binary metal halide perovskites offer a perfect opportunity for tuning optical bandgap and thus hold significant potential in emerging technologies such as solar cells. However, an easy oxidation of Sn2+ to Sn4+ has become one of the main issues for achieving efficient and stable Sn‐based perovskite solar cells (PSCs). Herein, an effective method for stabilizing CsPb0.5Sn0.5I2Br is proposed to realize high‐efficiency PSCs via antioxidant tea polyphenol (TP). It is found that TP can not only slow down the oxidation of Sn2+ but also regulate perovskite film crystallization during the formation of perovskite films via coordination interaction, leading to a reduced density of defects and an enlarged open‐circuit voltage. The resultant perovskite solar cell using CsPb0.5Sn0.5I2Br (TP) with an all‐inorganic mesoscopic framework of FTO/c‐TiO2/m‐TiO2/Al2O3/NiO/carbon achieves an impressive power conversion efficiency of 8.10% with high stability.
Low‐Temperature Oxidation‐Processed Titanium Oxides as Dual‐Functional Electron‐Selective Passivation Contacts
Authors: Wang Wei , Yang Zhenhai , Wang Zhixue , Lin Hao , Wang Jiajia , Liao Mingdun , Zeng Yuheng , Yan Baojie , Ye Jichun
Published: December 2019

Passivation contact (PSC), which simultaneously achieves high passivation quality and low contact resistivity, has been proven to be a delicate design to fabricate high‐efficiency solar cells (SCs). However, traditional PSC materials, that is, intrinsic a‐Si:H/doped a‐Si:H or tunnel SiO2/doped poly‐Si, overly rely on the complex procedures and have inevitable optical or Auger recombination losses. Herein, a novel low‐temperature oxidation (LTO) process is developed and an electron‐selective TiOx film (LTO‐TiOx) is fabricated, reaching a low‐effective surface recombination velocity of 13.7 cm s−1. The high‐quality passivation performance is mainly attributed to the chemical passivation of Ti–O–Si bonds and the surface carrier manipulation ability of the LTO‐TiOx film. Next, by adding a low work function (WF) layer of LiFx film, the surface band bending effect is formed and the contact resistivity of TiOx‐based PSC is also optimized. Furthermore, the dual‐functional LTO‐TiOx/LiFx electron‐selective PSC is integrated in Si SCs and a champion efficiency is achieved near 19% with an open‐circuit voltage near 640 mV. Finally, a comprehensive simulation analysis indicates a high efficiency of more than 22% based on LTO‐TiOx PSC, followed by a detailed roadmap of efficiency improvements, demonstrating its huge application potential in SCs.
Diagnosis of fetal defects in twin pregnancies at routine 11–13‐week ultrasound examination
Authors: Syngelaki A. , Cimpoca B. , Litwinska E. , Akolekar R. , Nicolaides K. H.
Published: December 2019

Objectives

To examine the performance of the routine 11–13‐week scan in detecting fetal defects in twin pregnancies and to examine if, in pregnancies with a fetal defect, compared to those with normal fetuses, there is increased incidence of nuchal translucency thickness (NT) ≥ 95th and ≥ 99th percentiles or intertwin discordance in crown–rump length (CRL) ≥ 10% and ≥ 15%.

Methods

This was a retrospective analysis of prospectively collected data in twin pregnancies undergoing routine ultrasound examination for fetal anatomy, according to standardized protocols, at 11–13 weeks' gestation between 2002 and 2019. Pregnancies with known chromosomal abnormality were excluded. The final diagnosis of fetal defect was based on the results of postnatal examination in cases of live birth and on the findings of the last ultrasound examination in cases of pregnancy termination, miscarriage or stillbirth. The performance of the 11–13‐week scan in the detection of fetal defects was determined.

Results

The study population of 6366 twin pregnancies with two live fetuses at 11–13 weeks' gestation included 4979 (78.2%) dichorionic (DC) and 1387 (21.8%) monochorionic (MC) twin pregnancies. The main findings were: first, the overall incidence of fetal defects was higher in MC than in DC twins (2.8% vs 1.3%); second, the proportion of defects diagnosed in the first trimester was higher in MC than in DC twins (52.6% vs 27.1%); third, the pattern of defects in relation to detectability at the 11–13‐week scan (always detectable, sometimes detectable and never detectable) was similar to that reported previously in singleton pregnancies; fourth, always‐detectable defects included acrania, alobar holoprosencephaly, encephalocele, pentalogy of Cantrell, exomphalos, body‐stalk anomaly, twin reversed arterial perfusion sequence and conjoined twins; fifth, the incidence of fetal NT ≥ 95th percentile was higher in those with than in those without a defect (16.5% vs 4.5% in DC twins and 19.2% vs 5.9% in MC twins) and this was also true for NT ≥ 99th percentile (8.3% vs 1.0% in DC twins and 15.4% vs 2.0% in MC twins); and sixth, the incidence of CRL discordance ≥ 10% was higher in those with than in those without a defect (20.2% vs 7.9% in DC twins and 33.8% vs 9.3% in MC twins) and this was also true for CRL discordance ≥ 15% (10.1% vs 1.9% in DC twins and 28.2% vs 2.8% in MC twins).

Conclusions

First, fetal defects are more common in MC than in DC twin pregnancies. Second, first‐trimester detection of fetal defects in DC twin pregnancies is similar to that in singleton pregnancies. Third, first‐trimester detectability of defects in MC twins is higher than in DC twins. Fourth, in twin pregnancies with a fetal defect, there is higher intertwin discordance in CRL and incidence of increased NT, but the predictive performance of screening by these markers is poor. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Insight into the siRNA transmembrane delivery—From cholesterol conjugating to tagging
Authors: Zheng Yan , Tai Wanyi
Published: December 2019

Small interfering RNA (siRNA), combining the features of unprecedented potency, target‐specificity, and the unique sequence‐based disease‐intervention model, has received immense considerations over the past decades in the academia and pharmaceutical industry. siRNA fits the criteria of being drug‐likely enough to meet with the therapeutic purpose, but its clinical translation has been impeded for a long time by the poor efficiency of in vivo delivery. To reach the cytosol where the RNA interference (RNAi) takes place, siRNA delivery faces a serial of systemic and cellular barriers, especially the endosomal sequestration that would prevent the majority of siRNA from cytosol entry. Transmembrane delivery of siRNA represents a new avenue for efficient delivery by bypassing the endosomal pathway. This rationale is bolstered by the high efficiency of viral entry by membrane fusion, but rarely pursued by artificial siRNA delivery systems. Here, this article provides an opinion of transmembrane delivery by hydrophobic modulation of siRNA. We give a brief introduction of the current siRNA delivery modes, including the hydrophobic cholesterol siRNA conjugates. The cholesterol tagging technology is design on the rationale of hydrophobic siRNAs approach, but hydrophobic modulation throughout the whole siRNA backbone for efficient membrane fusion and transmembrane delivery. The challenge and potential of this technology for preclinical development are also discussed.

This article is categorized under:

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Biology‐Inspired Nanomaterials > Lipid‐Based Structures

Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures
Prevention and Treatment of Atherosclerosis: The Use of Nutraceuticals and Functional Foods
Authors: Visioli Francesco , Poli Andrea
Published: December 2019

Nutritional interventions are effective and – in theory – easy to implement primary and secondary prevention strategies that reduce several risk factors of atherosclerosis and cardiovascular disease (CVD). Yet, because of (a) the severe impact of CVD in terms of mortality, morbidity, quality of life, and economy, (b) the proved role of LDL plasma concentrations as the most critical risk factor, and (c) the obstacles found both in terms of biological effects and compliance of the patient by an exclusively dietary intervention, food supplements or nutraceuticals are now valuable resources for physicians. As regards cholesterol control, several preparations are available in the market, and we will critically review them in this chapter.
Modelling the HIV-Associated TB Epidemic and the Impact of Interventions Aimed at Epidemic Control
Authors: Dodd P. J. , Pretorius C. , Williams B. G.
Published: December 2019

In this chapter, we focus on mathematical models of tuberculosis epidemiology (TB) that include interactions with HIV and an explicit representation of transmission. We review the natural history of TB and illustrate how its features are simplified and incorporated in mathematical models. We then review the ways HIV influences the natural history of TB, the interventions that have been considered in models, and the way these individual-level effects are represented in models. We then go on to consider population-level effects, reviewing the TB/HIV modelling literature. We first review studies whose focus was on purely epidemiological modelling, and then studies whose focus was on modelling the impact of interventions. We conclude with a summary of the uses and achievements of TB/HIV modelling and some suggested future directions.
Pharmacokinetics of methylphenidate and ritalinic acid in plasma correlations with exhaled breath and oral fluid in healthy volunteers
Authors: Arvidsson Michel , Dahl Marja-Liisa , Beck Olof , Ackehed Gerd , Nordin Karin , Rosenborg Staffan
Published: December 2019

Purpose

The primary aim of this study was to explore the potential of alternative sampling matrices for methylphenidate by assessing the correlations betweendl-threo-methylphenidate anddl-threo-ritalinic acid concentrations in exhaled breath and oral fluid with those in plasma, in repeated samples collected after a single oral dose of methylphenidate. The secondary aim was to study the enantioselective pharmacokinetics of methylphenidate in plasma, with a focus on interindividual variability in the metabolism of methylphenidate to ritalinic acid.

Methods

Twelve healthy volunteers received a single oral dose ofdl-threo-methylphenidate (Ritalin®capsules, 20 mg). Venous blood samples were collected for 24 h, and plasma analyzed forthreo-enantiomers of methylphenidate and ritalinic acid with LC-MS/MS. Repeated sampling of exhaled breath, using a particle filter device, and of non-stimulated oral fluid, using a felt pad device, was also performed. Exhaled breath and oral fluid were analyzed with a non-enantioselective LC-MS/MS method fordl-threo-methylphenidate anddl-threo-ritalinic acid.

Results

In all subjects,d-threo-methylphenidate was detectable in plasma for at least 15 h after the dose with a biphasic profile.l-threo-Methylphenidate was measurable in only five subjects and in most cases in low concentrations. However, one female subject displayed a biphasic concentration-time profile forl-threo-methylphenidate. This subject also had the highestd-threo-methylphenidate AUC (191 ng*h/mL versus 32–119 ng*h/mL in the other subjects).d-threo-Ritalinic acid concentrations were on average 25-fold higher (range 6–126) than the correspondingd-threo-methylphenidate concentrations. Single-time point plasma concentration ratios betweend-threo-ritalinic acid andd-threo-methylphenidate 1.5–12 h after dose correlated highly (r= 0.88–0.98) with thed-threo-ritalinic acid AUC/d-threo-methylphenidate AUC ratio. In eleven subjects,dl-threo-methylphenidate in oral fluid mirrored the biphasic profile of methylphenidate (sum ofd-andl-threo-enantiomers) in plasma, but the concentrations in oral fluid were on average 1.8 times higher than in plasma.dl-threo-Methylphenidate was detected in exhaled breath in all subjects, but there was no consistent concentration-time pattern.

Conclusions

In some subjects, the pharmacologically less activel-threo-enantiomer may contribute to the total plasma methylphenidate concentrations. Monitoring methylphenidate concentrations without enantiomeric determination carries the risk of missing such subjects, which might affect how the plasma concentrations of methylphenidate are interpreted and used for clinical decision making. The use of exhaled breath and oral fluid to assess medication adherence to MPH in patients with ADHD warrants further studies.
Diffusion-weighted imaging of the breast—a consensus and mission statement from the EUSOBI International Breast Diffusion-Weighted Imaging working group
Authors:   On behalf of the EUSOBI international Breast Diffusion-Weighted Imaging working group, Baltzer Pascal , Mann Ritse M. , Iima Mami , Sigmund Eric E. , Clauser Paola , Gilbert Fiona J. , Martincich Laura , Partridge Savannah C. , Patterson Andrew , Pinker Katja , Thibault Fabienne , Camps-Herrero Julia , Le Bihan Denis
Published: December 2019

The European Society of Breast Radiology (EUSOBI) established an International Breast DWI working group. The working group consists of clinical breast MRI experts, MRI physicists, and representatives from large vendors of MRI equipment, invited based upon proven expertise in breast MRI and/or in particular breast DWI, representing 25 sites from 16 countries. The aims of the working group are (a) to promote the use of breast DWI into clinical practice by issuing consensus statements and initiate collaborative research where appropriate; (b) to define necessary standards and provide practical guidance for clinical application of breast DWI; (c) to develop a standardized and translatable multisite multivendor quality assurance protocol, especially for multisite research studies; (d) to find consensus on optimal methods for image processing/analysis, visualization, and interpretation; and (e) to work collaboratively with system vendors to improve breast DWI sequences. First consensus recommendations, presented in this paper, include acquisition parameters for standard breast DWI sequences including specifications of b values, fat saturation, spatial resolution, and repetition and echo times. To describe lesions in an objective way, levels of diffusion restriction/hindrance in the breast have been defined based on the published literature on breast DWI. The use of a small ROI placed on the darkest part of the lesion on the ADC map, avoiding necrotic, noisy or non-enhancing lesion voxels is currently recommended. The working group emphasizes the need for standardization and quality assurance before ADC thresholds are applied. The working group encourages further research in advanced diffusion techniques and tailored DWI strategies for specific indications.

Key Points

• The working group considers breast DWI an essential part of a multiparametric breast MRI protocol and encourages its use.

• Basic requirements for routine clinical application of breast DWI are provided, including recommendations on b values, fat saturation, spatial resolution, and other sequence parameters.

• Diffusion levels in breast lesions are defined based on meta-analysis data and methods to obtain a reliable ADC value are detailed.
Changes of trace element status during aging: results of the EPIC-Potsdam cohort study
Authors: Baudry Julia , Kopp Johannes F. , Boeing Heiner , Kipp Anna P. , Schwerdtle Tanja , Schulze Matthias B.
Published: December 2019

Purpose

We aimed to evaluate age-dependent changes of six trace elements (TE) [manganese (Mn), iron (Fe), zinc (Zn), copper (Cu), iodine (I), and selenium (Se)] over a 20-year period.

Methods

TE concentrations were determined using repeated serum samples taken at baseline and after 20 years of follow-up from 219 healthy participants of the EPIC-Potsdam study, using inductively coupled plasma tandem mass spectrometry. For each TE, absolute and relative differences were calculated between the two time points, as well as the proportion of individuals within normal reference ranges. Interdependence between age-related TE differences was investigated using principal component analysis (PCA). Relationships between selected factors (lifestyle, sociodemographic, anthropometric factors, and hypertension) and corresponding TE longitudinal variability were examined using multivariable linear regression models.

Results

Median age of our study sample was 58.32 years (4.42) at baseline and 40% were females. Median Mn, Zn, Se concentrations and Se to Cu ratio significantly decreased during aging while median Fe, Cu, I concentrations and Cu to Zn ratio significantly increased. A substantial percentage of the participants, at both time points, had Zn concentrations below the reference range. The first PCA-extracted factor reflected the correlated decline in both Mn and Zn over time while the second factor reflected the observed (on average) increase in both Cu and I over time. Overall, none of the investigated factors were strong determinants of TE longitudinal variability, except possibly dietary supplement use, and alcohol use for Fe.

Conclusions

In conclusion, in this population-based study of healthy elderly, decrease in Mn, Zn, and Se concentrations and increase in Fe, Cu, and I concentrations were observed over 20 years of follow-up. Further research is required to investigate dietary determinants and markers of TE status as well as the relationships between TE profiles and the risk of age-related diseases.
Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma
Authors: Xu Enhong , Liang Xiaoben , Ji Zhenhua , Zhao Shuwei , Li Li , Lang Juntian
Published: December 2019

Purpose

The long non-coding RNA MALAT1 is a predictive marker in several solid tumors with highly conserved sequences. However, the role of non-coding RNA in development of laryngeal or hypopharyngeal cancer remains unclear.

Methods

Tumor tissues and adjacent non-cancer tissues of 24 patients were collected. We detected the expression of MALAT1 in laryngeal cancer tissues and hypopharyngeal cancer tissues. Moreover, we developed a MALAT1 silencing model in human laryngeal tumor cells by transfecting MALAT1 small interfering RNA into human laryngeal carcinoma cell line Hep-2 and pharyngeal carcinoma cell line FaDu with Lipofectamine 2000 system. Cell cycle analysis, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, and wound-healing assays were performed to evaluate the impact of MALAT1 depletion on laryngeal or hypopharyngeal cancer cell’s growth, proliferation, apoptosis, invasion and migration.

Results

MALAT1 was significantly up-regulated in laryngeal and hypopharyngeal carcinoma cells. MALAT1 down-regulation induced the increased apoptosis of both cell lines and suppressed cells’ proliferation. Cells were arrested in G1/G2 phase and cells of S phase were significantly decreased. Down-regulation of MALAT1 expression can also inhibit the migration and invasion of laryngeal squamous cell carcinoma cell (Hep-2) and hypopharyngeal cancer cell (FaDu).

Conclusion

In summary, our deactivation model of MALAT1 disentangled the active function of it as a regulator of gene expression governing the hallmarks of laryngeal and hypopharyngeal cancer. Blocking this long non-coding RNA may restrain the development of laryngeal cancer.
Hospital volume and outcome in inguinal hernia repair: analysis of routine data of 133,449 patients
Authors: Maneck M. , Köckerling F. , Fahlenbrach C. , Heidecke C. D. , Heller G. , Meyer H. J. , Rolle U. , Schuler E. , Waibel B. , Jeschke E. , Günster C.
Published: December 2019

Introduction

Inguinal hernias are repaired using either open or minimally invasive surgical techniques. For both types of surgery it has been demonstrated that a higher annual surgeon volume is associated with a lower risk of recurrence. This present study investigated the volume-outcome implications for recurrence operations, surgical complications, rate of chronic pain requiring treatment, and 30-day mortality based on the hospital volume.

Materials and methods

The data basis used was the routine data collected throughout the Federal Republic of Germany for persons insured by the Local General Sickness Fund “AOK” who had undergone inpatient inguinal hernia repair between 2013 and 2015. Complications were recorded by means of indicators. Hospitals were divided into five groups on the basis of the annual caseload volume: 1–50, 51–75, 76–100, 101–125, and ≥ 126 inguinal hernia repairs per year. The effect of the hospital volume on the indicators was assessed using multiple logistic regression.

Results

133,449 inguinal hernia repairs were included. The incidence for recurrence operations was 0.95%, for surgical complications 4.22%, for chronic pain requiring treatment 2.87%, and for the 30-day mortality 0.28%. Low volume hospitals (1–50 and 51–75 inguinal hernia repairs per year) showed a significantly increased recurrence risk compared to high volume hospitals with ≥ 126 inguinal hernia repairs per year (odds ratio: 1.53 and 1.24). No significant correlations were found for the other results.

Conclusions

The study gives a detailed picture of hospital care for inguinal hernia repair in Germany. Furthermore, it was noted that the risk of hernia recurrence decreases in line with a rising caseload of the treating hospital.
Impact of thrombocytes, on bacterial growth and antimicrobial activity of selected antibiotics
Authors: Nussbaumer-Pröll Alina Karoline , Eberl Sabine , Reiter Birgit , Stimpfl Thomas , Jäger Walter , Poschner Stefan , Zeitlinger Markus
Published: December 2019

In vitro pharmacodynamic models are used to optimize in vivo dosing regimens in antimicrobial drug development. One limiting factor of such models is the lack of host factors such as corpuscular blood components as erythrocytes which have already been shown to impact activity of antibiotics and/or growth of the pathogen. However, the impact of thrombocytes has not previously been investigated. We set out to investigate if the addition of thrombocytes (set to physiological concentrations in blood of healthy human, i.e., 5 × 105 thrombocytes/μL standard growth media Mueller Hinton Broth, MHB) has an influence on bacterial growth and on the efficacy of antibiotics against Gram+ and Gram− bacteria. Growth assays and time-killing-curves (TKC) were performed with ATCC-strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa in triplicate over 24 h. The same approach was followed for 5 clinical isolates of Escherichia coli. Meropenem, ciprofloxacin, and tigecycline were tested as representatives of broad-spectrum antibiotics, and concentrations several-fold above and below the minimal inhibitory concentration (MIC) were simulated. No significant impact of thrombocytes was found on bacterial growth or antimicrobial stability for the investigated agents. Bacteria reduced thrombocyte content to different degree, indicating direct interaction of pathogens and thrombocytes. Impact on bacterial killing was observed but was not fully reproducible when thrombocytes from different donors where used. While interaction of bacteria and thrombocytes was evident in the present study, interaction between antibiotic activity and thrombocytes seems unlikely. Whether variability was caused by different thrombocyte concentrates needs further investigation.
Work functions shaping the ability to innovate: insights from the case of the safety engineer
Authors: Asplund Fredrik , Ulfvengren Pernilla
Published: December 2019

To perform as intended, firms are divided into work functions that contribute to the behaviour-shaping constraints under which individuals build their skills, knowledge and networks. These in turn provide a specialized perspective on organisational structure and culture. In a mixed methods study involving interviews and statistical analyses, we investigate whether a work function can thereby affect individuals’ innovation foci and efficacy. Safety engineers, central to firms developing Cyber-Physical Systems (CPS), are shown to play a significant role in identifying and supporting viable innovation related to organisational aspects. Results indicate that safety engineers could use the firm’s collaborative innovation process to facilitate organisational learning, helping different work functions come together to construct working practices aligned with the organisational values of the firm. This is explained by their understanding of safety culture—a specialized understanding of organisational culture and complexity provided by their work function. We conclude that work functions that provide their members with a perspective well aligned with their firm’s organisational values can instil the ability to identify and support organisational innovation. This suggests that safety engineers in CPS domains could be effective in a mediatory role, facilitating innovative changes to organisational structures and processes when introducing and operating safety management systems. Stronger aspects of organisational liaising and systems thinking could reinforce this ability—the former by a wider scope and motivation leading to an increased skill in communicating with dissimilar individuals, and the latter by providing the skills and tools needed to analyse the politics of complex organisations.
Human Auditory Detection and Discrimination Measured with the Pupil Dilation Response
Authors: Bala Avinash D. S. , Whitchurch Elizabeth A. , Takahashi Terry T.
Published: December 2019

In the standard Hughson-Westlake hearing tests (Carhart and Jerger 1959), patient responses like a button press, raised hand, or verbal response are used to assess detection of brief test signals such as tones of varying pitch and level. Because of its reliance on voluntary responses, Hughson-Westlake audiometry is not suitable for patients who cannot follow instructions reliably, such as pre-lingual infants (Northern and Downs 2002). As an alternative approach, we explored the use of the pupillary dilation response (PDR), a short-latency component of the orienting response evoked by novel stimuli, as an indicator of sound detection. The pupils of 31 adult participants (median age 24 years) were monitored with an infrared video camera during a standard hearing test in which they indicated by button press whether or not they heard narrowband noises centered at 1, 2, 4, and 8 kHz. Tests were conducted in a quiet, carpeted office. Pupil size was summed over the first 1750 ms after stimulus delivery, excluding later dilations linked to expenditure of cognitive effort (Kahneman and Beatty 1966; Kahneman et al. 1969). The PDR yielded thresholds comparable to the standard test at all center frequencies tested, suggesting that the PDR is as sensitive as traditional methods of assessing detection. We also tested the effects of repeating a stimulus on the habituation of the PDR. Results showed that habituation can be minimized by operating at near-threshold stimulus levels. At sound levels well above threshold, the PDR habituated but could be recovered by changing the frequency or sound level, suggesting that the PDR can also be used to test stimulus discrimination. Given these features, the PDR may be useful as an audiometric tool or as a means of assessing auditory discrimination in those who cannot produce a reliable voluntary response.
High-level expression of highly active and thermostable trehalase from Myceliophthora thermophila in Aspergillus niger by using the CRISPR/Cas9 tool and its application in ethanol fermentation
Authors: Dong Liangbo , Lin Xiaotong , Yu Dou , Huang Lianggang , Wang Bin , Pan Li
Published: December 2019

Trehalase catalyzes the hydrolysis of the non-reducing disaccharide trehalose. The highly active trehalase MthT from Myceliophthora thermophila was screened from the trehalase genes of six species of filamentous fungi. An ingenious multi-copy knock-in expression strategy mediated by the CRISPR/Cas9 tool and medium optimization were used to improve MthT production in Aspergillus niger, up to 1698.83 U/mL. The protein background was dramatically abated due to insertion. The recombinant MthT showed optimal activity at pH 5.5 and 60 °C, and exhibited prominent thermal stability between 50 and 60 °C under acid conditions (pH 4.5–6.5). The ethanol conversion rate (ethanol yield/total glucose) was significantly improved by addition of MthT (51.88%) compared with MthT absence (34.38%), using 30% starch saccharification liquid. The results of this study provided an effective strategy, established a convenient platform for heterologous expression in A. niger and showed a potential strategy to decrease production costs in industrial ethanol production.
Analysis and control of max-plus linear discrete-event systems: An introduction
Authors: De Schutter Bart , van den Boom Ton , Xu Jia , Farahani Samira S.
Published: December 2019

The objective of this paper is to provide a concise introduction to the max-plus algebra and to max-plus linear discrete-event systems. We present the basic concepts of the max-plus algebra and explain how it can be used to model a specific class of discrete-event systems with synchronization but no concurrency. Such systems are called max-plus linear discrete-event systems because they can be described by a model that is “linear” in the max-plus algebra. We discuss some key properties of the max-plus algebra and indicate how these properties can be used to analyze the behavior of max-plus linear discrete-event systems. Next, some control approaches for max-plus linear discrete-event systems, including residuation-based control and model predictive control, are presented briefly. Finally, we discuss some extensions of the max-plus algebra and of max-plus linear systems.