bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility of 177Lu‐DOTATATE PRRT in somatostatin receptor‐positive metastatic medullary carcinoma of thyroid patients with assessment of efficacy, survival analysis, prognostic variables, and toxicity
Authors: Parghane Rahul V. , Naik Chinna , Talole Sanjay , Desmukh Anuja , Chaukar Devendra , Banerjee Sharmila , Basu Sandip
Published: November 2019

Background

The primary aim of this study was to evaluate the therapeutic efficacy and outcome of 177Lu‐DOTATATE peptide receptor radionuclide therapy (PRRT) in somatostatin receptor‐positive metastatic medullary thyroid carcinoma (MTC), including progression‐free survival (PFS) and overall survival (OS), and also to determine the various prognostic variables. The secondary aim was toxicity assessment of PRRT in this group of patients.

Methods

A total of 43 somatostatin receptor‐positive metastatic MTC patients, treated with 177Lu‐DOTATATE PRRT in a large tertiary care center, were included in this analysis. After receiving the therapy, post‐treatment response evaluation was undertaken for symptomatic and biochemical responses (serum calcitonin) and imaging responses with 68Ga‐DOTATATE, 18F‐FDG PET‐CT, CeCT (PERCIST and RECIST 1.1 criteria). Calcitonin doubling time (CtnDT) was calculated by the American Thyroid Association calculator. The adverse events were graded according to the NCI‐CTCAE v5.0 criteria. The observed Kaplan‐Meier curves for both PFS and OS since first PRRT were compared with CtnDT (more than 24 months vs less than 24 months) by log‐rank (Mantel‐Cox) test. The prognostic variables were investigated for their association with CtnDT and response to PRRT using Cox proportional‐hazards model.

RESULTS

The median OS was 26 months (95% CI 16.6‐35.3 months) and the median PFS 24 months (95%.CI: 15.1‐32.9 months). Following 177Lu‐DOTATATE PRRT, the observed median PFS and OS was longer in patients who had CtnDT more than 24 months compared to those with CtnDT less than 24 months (median PFS not yet reached vs 10 months and median OS 60 months vs 20 months). Assessing from the time‐point of first 177Lu‐DOTATATE PRRT cycle, the patients with CtnDT more than 24 months had a significantly longer PFS (P < .001) and OS (P < .001) compared to those with less than 24 months. Less than 5 lesions, FDG uptake in lesions (SUVmax of <5) and patients alive at the time of analysis were the significant variables for association with CtnDT (more than 24 months). Out of 43 patients, 26 were responders (61%) and 17 nonresponders (39%) based upon PERCIST criteria, and 27 were responders (62%) while 16 patients were nonresponders (38%) based upon RECIST 1.1 criteria. The univariate analysis showed significant association between responses to PRRT with following prognostic variables: (a) size of lesions (<2 cm) and (b) FDG uptake in lesions (SUVmax of <5). PRRT was well tolerated in all patients without any major grade 3 or 4 toxicity.

Conclusion

The results demonstrated that, 177Lu‐DOTATATE is a potentially efficacious and safe therapeutic option in SSTR avid metastatic MTC patients.
Hormone‐related diseases and prostate cancer: An English national record linkage study
Authors: Watts Eleanor L. , Goldacre Raphael , Key Timothy J. , Allen Naomi E. , Travis Ruth C. , Perez‐Cornago Aurora
Published: November 2019

Insulin‐like growth factor‐I (IGF‐I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF‐I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow‐up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal‐associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09–1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92–2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37–0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35–0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF‐I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.
Regime switches and permanent changes in impacts of housing risk factors on MSA‐level housing returns
Authors: Huang MeiChi
Published: November 2019

This study assesses impacts of housing risk factors on metropolitan housing excess returns in the augmented housing pricing model. Credit and liquidity factors represent demand and supply sides, respectively, of housing markets. All metropolitan statistical areas have significant regime switches, and booms and busts are turbulent and influenced by the two factors. The explanatory powers of the liquidity factor shrivel for the boom‐bust and regime‐switching volatility specifications, and excess housing returns are less sensitive to nationwide housing dynamics after 2008. This study lends support to time‐varying exposures of housing excess returns to risk factors in terms of temporary switches and permanent changes.
Synthesis, antiradical, and antimicrobial activities of new pteridine‐2,4,7‐trione derivatives
Authors: Kazunin Maksym S. , Voskoboynik Oleksii Yu. , Nosulenko Inna S. , Berest Galina G. , Kholodniak Sergiy V. , Pryymenko Boris O. , Kovalenko Sergiy I.
Published: November 2019

The synthesis of 6‐(2‐hydroxy‐2‐aryl (heteryl)ethyl)‐1‐methylpteridine‐2,4,7(1H,3H,8H)‐triones by the reduction of the corresponding ketones and the peculiarities of conversion of the synthesized alcohols to (E)‐1‐methyl‐6‐(2‐aryl (heteryl)ethenyl)pteridine‐2,4,7(1H,3H,8H)‐triones was reported. The mechanism of monomolecular elimination that occurred in the presence of hydrogen halides was discussed, namely, the competitive formation of an energy‐efficient conjugated system by deprotonation of a stable benzyl‐type carbocation. Alternative synthesis methods of pteridine‐2,4,7(1H,3H,8H)‐triones were developed. Abovementioned approach involved [4+2]‐cyclocondensation of 1‐methyl‐5,6‐diaminouracil to 2‐oxo‐4‐R‐but‐3‐enoic acids and Knoevenagel condensation of 1,6‐dimethylpteridine‐2,4,7(1H,3H,8H)‐trione with aromatic aldehydes. The antiradical, antimicrobial, and antifungal activities were studied for the synthesized compounds.
Improvements in Metabolic Syndrome by Xanthohumol Derivatives Are Linked to Altered Gut Microbiota and Bile Acid Metabolism
Authors: Zhang Yang , Bobe Gerd , Revel Johana S. , Rodrigues Richard R. , Sharpton Thomas J. , Fantacone Mary L. , Raslan Kareem , Miranda Cristobal L. , Lowry Malcolm B. , Blakemore Paul R. , Morgun Andrey , Shulzhenko Natalia , Maier Claudia S. , Stevens Jan F. , Gombart Adrian F.
Published: November 2019

Scope

Two hydrogenated xanthohumol (XN) derivatives, α,β‐dihydro‐XN (DXN) and tetrahydro‐XN (TXN), improved parameters of metabolic syndrome (MetS), a critical risk factor of cardiovascular disease (CVD) and type 2 diabetes, in a diet‐induced obese murine model. It is hypothesized that improvements in obesity and MetS are linked to changes in composition of the gut microbiota, bile acid metabolism, intestinal barrier function, and inflammation.

Methods and results

To test this hypothesis, 16S rRNA genes were sequenced and bile acids were measured in fecal samples from C57BL/6J mice fed a high‐fat diet (HFD) or HFD containing XN, DXN or TXN. Expression of genes associated with epithelial barrier function, inflammation, and bile acid metabolism were measured in the colon, white adipose tissue (WAT), and liver, respectively. Administration of XN derivatives decreases intestinal microbiota diversity and abundance—specifically Bacteroidetes and Tenericutes—alters bile acid metabolism, and reduces inflammation. In WAT, TXN supplementation decreases pro‐inflammatory gene expression by suppressing macrophage infiltration. Transkingdom network analysis connects changes in the microbiota to improvements in MetS in the host.

Conclusion

Changes in the gut microbiota and bile acid metabolism may explain, in part, the improvements in obesity and MetS associated with administration of XN and its derivatives.
A switchable dual‐mode fully‐differential common‐source low‐noise amplifier in 0.18‐μm CMOS technology
Authors: Zhang Changchun , Wang Yongkai , Gao Shenjun , Tang Lu , Zhang Yi , Park Sung Min
Published: November 2019

A highly‐integrated switchable dual‐mode low‐noise amplifier (LNA) is proposed and implemented in standard 0.18 μm complementary metal‐oxide‐semiconductor (CMOS) technology for ultra‐high frequency‐radio‐frequency identification (UHF RFID) reader receivers. This dual‐mode LNA can be controlled to operate in two different modes in order to meet the requirements for the listen‐before‐talk mode and the normal mode of the UHF RFID reader receiver, respectively. The fully‐differential common‐source cascode topology with perfect input impedance matching, capacitive cross‐coupling, and common‐mode feedback techniques are employed to improve its performance. Measurement results show that, from a single power supply of 1.8 V, the LNA achieved the power gain (S21) of 9.1 dB, the input power reflection (S11) of −20 dB, the minimum noise figure (NF) of 3.6 dB, and the P1dB of −5 dBm in high‐gain mode. In high‐linearity mode, S21 of 3.2 dB, S11 of −17 dB, NF of 5.2 dB, and P1dB of −1.3 dBm were obtained.
The limited efficacy of 3D models for teaching students sex estimations based on cranial traits: A case for investment in osteology teaching labs
Authors: Kuzminsky Susan C. , Snyder Thomas J. , Tung Tiffiny A.
Published: November 2019

The use of 3D digital imaging methods has increased within biological anthropology and medical research. Although digital renderings can be easily shared by researchers or used for student learning modules in osteology, limitations to using 3D models exist, requiring institutions of higher learning to invest in real bones or casts of human skeletal remains for labs. Here, we examine whether 3D digital models are viable proxies for real bones by testing the reliability of scoring sexually dimorphic traits of the human skull, a method commonly used by North American skeletal biologists. Forty‐five crania from Peruvian archaeological sites were used to score four sexually dimorphic cranial traits. These morphological traits were scored by one student learning osteology and an experienced researcher using the actual crania and 3D models of the same individuals. Statistical tests of rater agreement and strength of the agreement were conducted.

Results showed lower agreement between the actual and 3D scores for the student and higher agreement among the scores for the experienced researcher. Accurate and cost‐effective 3D models can serve as excellent replacements for real skeletal remains when researchers are experienced. However, 3D models may be a less reliable training tool for students learning osteological methods that require palpating areas of the human cranium. This study makes a strong case for purchasing quality casts or real human skeletal remains of legal/ethical origin for osteology teaching labs, despite their higher costs.
Study on stable detonation flame arrester test
Authors: Wang Peng , Bao Lei , Li Houda , Dang Wenyi , Yu Anfeng
Published: November 2019

Stable detonation flame arresters with nominal diameters from DN50 to DN300 were tested in accordance with the ISO 16852 standard, and the criteria for determining steady detonation were studied. According to the results of flame arrester tests, using the inner diameter of the pipeline as the basis for the pressure division yielded more accurate results, which was not clearly described in ISO 16852 standard. The target values of Pmd/PTB for the DN50 flame arrester were too small. Further studies are needed to determine appropriate ratios of Pmd/PTB for flame arresters with different pipe diameters. The run‐up distance required to form stable detonation was beyond L = 120 D, which is commonly believed to be the required distance for stable detonation to establish. Therefore, it is important to evaluate the conditions where flame arresters to be used and the conditions under which the flame arresters were tested.
Identification of active sequences in human laminin α5 G domain
Authors: Kumai Jun , Yamada Yuji , Hamada Keisuke , Katagiri Fumihiko , Hozumi Kentaro , Kikkawa Yamato , Nomizu Motoyoshi
Published: November 2019

Human laminin‐511 (α5β1γ1) and its truncated protein, laminin‐511 E8 fragment, bind to integrin α6β1 and have been widely used for embryonic stem cell and induced pluripotent stem cell culture under feeder‐free conditions. In this study, we focused on human laminin α5 chain G domain, which is thought to be critical for the biological functions of laminin‐511, and screened its biologically active sequences using a synthetic peptide library. We synthesized 115 peptides (hA5G1‐hA5G115) covering the entire laminin α5 chain G domain and evaluated cell attachment activity using both the peptide‐coated plate and peptide‐chitosan matrix (peptide‐ChtM) assays. Seventeen peptides demonstrated cell attachment activity in the assays. Both hA5G18 and hA5G26‐coated plates and hA5G74‐ChtMs promoted integrin β1‐mediated cell attachment. These findings are useful for the study of molecular mechanisms of laminin‐511, and the active peptides have a potential for use as a molecular probe for cell adhesion receptors.
Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain
Authors: Garrido‐Suárez Bárbara B. , Garrido Gabino , Piñeros Octavio , Delgado‐Hernández René
Published: November 2019

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such asMangifera indicaL. Previous studies have documented its analgesic, anti‐inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.
Increasing clinical liquid chromatography/tandem mass spectrometry assay throughput using a full calibration curve generated by one injection from a single‐tube calibrator
Authors: Cournoyer Jason J. , Dey Subhakar
Published: November 2019

Rationale

Mass spectrometry (MS) generally delivers more accurate results than immunoassay (IA) for certain clinically relevant analytes, but IA is still the more prevalent methodology used by clinical laboratories because of barriers to MS adoption, such as lower throughput. Therefore, it is increasingly important to develop new strategies to increase LC/MS/MS throughput so that more accurate results can be delivered to patients and clinicians.

Methods

Throughput can be increased by reducing assay calibration time using a single‐tube calibrator, a mix of isotopologues of the target analyte at different concentrations in a biological matrix, rather than a set of traditional, multiple‐tube calibrators. One injection from a single‐tube calibrator can generate a full calibration curve such that each calibration point is from the multiple reaction monitoring (MRM) signal corresponding to a specific isotopologue.

Results

In this study, a single‐tube calibrator (five levels in one vial) and a set of multiple‐tube calibrators (seven levels in seven vials) were used to measure the concentration of testosterone in 42 serum samples originally value assigned by the Centers for Disease Control and Prevention (CDC) reference method. The bias between the CDC reference method and the single‐tube calibrator measurements and the multiple‐tube calibrators measurements was +1.1% and − 5.5%, respectively. These results were within the CDC Hormone Standardization (HoSt) program bias acceptance criteria of ±6.4%.

Conclusions

The results show that LC/MS/MS throughput can be increased using a single‐tube calibrator because it reduces assay calibration time while delivering equivalent results to those generated using traditional, multiple‐tube calibrators. The single‐tube calibrator may also save cost to laboratories through reductions in consumable consumption, technician labor time, and inventory management, as well as to manufacturers because fewer vials would need to be manufactured, tested, stored, and shipped.
Self‐Assembly of DNA Origami Heterodimers in High Yields and Analysis of the Involved Mechanisms
Authors: Sheheade Breveruos , Liber Miran , Popov Mary , Berger Yaron , Khara Dinesh C. , Jopp Jürgen , Nir Eyal
Published: November 2019

Efficient fabrication of structurally and functionally diverse nanomolecular devices and machines by organizing separately prepared DNA origami building blocks into a larger structure is limited by origami attachment yields. A general method that enables attachment of origami building blocks using ‘sticky ends' at very high yields is demonstrated. Two different rectangular origami monomers are purified using agarose gel electrophoresis conducted in solute containing 100 × 10−3 m NaCl, a treatment that facilitates the dissociation of most of the incorrectly hybridized origami structures that form through blunt‐end interactions during the thermal annealing process and removes these structures as well as excess strands that otherwise interfere with the desired heterodimerization reaction. Heterodimerization yields of gel‐purified monomers are between 98.6% and 99.6%, considerably higher than that of monomers purified using the polyethylene glycol (PEG) method (88.7–96.7%). Depending on the number of PEG purification rounds, these results correspond to about 4‐ to 25‐fold reduction in the number of incorrect structures observed by atomic force microscopy. Furthermore, the analyses of the incorrect structures observed before and after the heterodimerization reactions and comparison of the purification methods provide valuable information on the reaction mechanisms that interfere with heterodimerization.
Diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy: a comparison of motion-compensated spin echo and stimulated echo techniques
Authors: Khalique Zohya , Scott Andrew D. , Ferreira Pedro F. , Nielles-Vallespin Sonia , Firmin David N. , Pennell Dudley J.
Published: November 2019

Objectives

Diffusion tensor cardiovascular magnetic resonance (DT-CMR) interrogates myocardial microstructure. Two frequently used in vivo DT-CMR techniques are motion-compensated spin echo (M2-SE) and stimulated echo acquisition mode (STEAM). Whilst M2-SE is strain-insensitive and signal to noise ratio efficient, STEAM has a longer diffusion time and motion compensation is unnecessary. Here we compare STEAM and M2-SE DT-CMR in patients.

Materials and methods

Biphasic DT-CMR using STEAM and M2-SE, late gadolinium imaging and pre/post gadolinium T1-mapping were performed in a mid-ventricular short-axis slice, in ten hypertrophic cardiomyopathy (HCM) patients at 3 T.

Results

Adequate quality data were obtained from all STEAM, but only 7/10 (systole) and 4/10 (diastole) M2-SE acquisitions. Compared with STEAM, M2-SE yielded higher systolic mean diffusivity (MD) (p = 0.02) and lower fractional anisotropy (FA) (p = 0.02, systole). Compared with segments with neither hypertrophy nor late gadolinium, segments with both had lower systolic FA using M2-SE (p = 0.02) and trend toward higher MD (p = 0.1). The negative correlation between FA and extracellular volume fraction was stronger with STEAM than M2-SE (r2 = 0.29, p < 0.001 STEAM vs. r2 = 0.10, p = 0.003 M2-SE).

Discussion

In HCM, only STEAM reliably assesses biphasic myocardial microstructure. Higher MD and lower FA from M2-SE reflect the shorter diffusion times. Further work will relate DT-CMR parameters and microstructural changes in disease.
Wildlife Management, Species Injustice and Ecocide in the Anthropocene
Authors: Sollund Ragnhild
Published: November 2019

Norway has been signatory to the Council of Europe’s Convention on the Conservation of European Wildlife and Natural Habitats (1979) (otherwise known as the “Bern Convention”) since 1986. Nevertheless, every year, Norwegian authorities authorize the killing of brown bears, lynx, wolves and wolverines, which are listed as strictly protected fauna species by the Bern Convention. Norway has a responsibility to protect these species and has several times been brought to court by nongovernmental organizations (NGOs) for failure to satisfy their duties under this international legal instrument. This article discusses Norway’s large predator policy and its compliance with the Bern Convention through an analysis of court decisions and judicial reasoning from the perspective of species justice for nonhumans.
SIAS-miner: mining subjectively interesting attributed subgraphs
Authors: Bendimerad Anes , Mel Ahmad , Lijffijt Jefrey , Plantevit Marc , Robardet Céline , De Bie Tijl
Published: November 2019

Data clustering, local pattern mining, and community detection in graphs are three mature areas of data mining and machine learning. In recent years, attributed subgraph mining has emerged as a new powerful data mining task in the intersection of these areas. Given a graph and a set of attributes for each vertex, attributed subgraph mining aims to find cohesive subgraphs for which (some of) the attribute values have exceptional values. The principled integration of graph and attribute data poses two challenges: (1) the definition of a pattern syntax (the abstract form of patterns) that is intuitive and lends itself to efficient search, and (2) the formalization of the interestingness of such patterns. We propose an integrated solution to both of these challenges. The proposed pattern syntax improves upon prior work in being both highly flexible and intuitive. Plus, we define an effective and principled algorithm to enumerate patterns of this syntax. The proposed approach for quantifying interestingness of these patterns is rooted in information theory, and is able to account for background knowledge on the data. While prior work quantified the interestingness for the cohesion of the subgraph and for the exceptionality of its attributes separately, then combining these in a parameterized trade-off, we instead handle this trade-off implicitly in a principled, parameter-free manner. Empirical results confirm we can efficiently find highly interesting subgraphs.
A Stochastic Graphs Semantics for Conditionals
Authors: Wójtowicz Krzysztof , Wójtowicz Anna
Published: November 2019

We define a semantics for conditionals in terms of stochastic graphs which gives a straightforward and simple method of evaluating the probabilities of conditionals. It seems to be a good and useful method in the cases already discussed in the literature, and it can easily be extended to cover more complex situations. In particular, it allows us to describe several possible interpretations of the conditional (the global and the local interpretation, and generalizations of them) and to formalize some intuitively valid but formally incorrect considerations concerning the probabilities of conditionals under these two interpretations. It also yields a powerful method of handling more complex issues (such as nested conditionals). The stochastic graph semantics provides a satisfactory answer to Lewis’s arguments against the PC = CP principle, and defends important intuitions which connect the notion of probability of a conditional with the (standard) notion of conditional probability. It also illustrates the general problem of finding formal explications of philosophically important notions and applying mathematical methods in analyzing philosophical issues.
The Role of Cortico-Thalamo-Cortical Circuits in Language: Recurrent Circuits Revisited
Authors: Crosson Bruce
Published: November 2019

Based on a review of recent literature, a recurrent circuit model describes how cortico-thalamo-cortical and cortico-cortical circuitry supports word retrieval, auditory-verbal comprehension, and other language functions. Supporting data include cellular and layer-specific cortico-thalamic, thalamo-cortical, and cortico-cortical neuroanatomy and electrophysiology. The model posits that during word retrieval, higher order cortico-thalamo-cortical relays maintain stable representations of semantic information in feedforward processes at the semantic-lexical interface. These stable semantic representations are compared to emerging lexical solutions to represent the semantic construct to determine how well constructs are associated with each other. The resultant error signal allows cortico-cortical sculpting of activity between the semantic and lexical mechanisms until there is a good match between these two levels, at which time the lexical solution will be passed along to the cortical processor necessary for the next stage of word retrieval. Evidence is cited that high gamma activity is the neural signature for processing in the cortico-thalamo-cortical and cortico-cortical circuitry. Methods for testing hypotheses generated from this recurrent circuit model are discussed. Mathematical modeling may be a useful tool in exploring underlying properties of these circuits.
Children’s Encounters with Natural Selection During an Interactive Read Aloud
Authors: Frejd Johanna
Published: November 2019

Previous studies have shown that children as young as 5 years of age are able to form a basic understanding of evolution after listening to a storybook about natural selection. This study offers a semiotic exploration of children’s meaning making during an interactive read aloud of the same storybook by investigating what children focus on and negotiate during the read aloud. Video data from eight interactive read aloud sessions (N = 24 children) were analysed using a multimodal approach and contrasted with seven biological concepts intentionally described in the storybook. During the interactive reading, the children focused on all biological concepts at some point. However, apart from the biological concepts, the children also paid attention to other topics during the read aloud. These topics comprised Death, Change in behaviour, Realism, Babies, Milli bugs, and Aesthetics. Throughout the read aloud, a child-centric view of life influenced how the children made meaning about evolution. The findings highlight that through interactive reading, instructional storybooks also become a tool for discussing other aspects that children find important. Overall, the findings contribute with knowledge about the role of interactive read aloud as a pedagogical tool for introducing evolution in early childhood education.
Application of cellulose-based polymers in oil well cementing
Authors: Abbas Ghulam , Irawan Sonny , Memon Khalil Rehman , Khan Javed
Published: November 2019

Cellulose-based polymers have been successfully used in many areas of petroleum engineering especially in enhanced oil recovery drilling fluid, fracturing and cementing. This paper presents the application of cellulose-based polymer in oil well cementing. These polymers work as multifunctional additive in cement slurry that reduce the quantity of additives and lessen the operational cost of cementing operation. The viscosity of cellulose polymers such as hydroxyethyl cellulose (HEC), carboxymethylcellulose (CMC) and hydroxypropyl methylcellulose (HPMC) has been determined at various temperatures to evaluate the thermal degradation. Moreover, polymers are incorporated in cement slurry to evaluate the properties and affect in cement slurry at 90 °C. The API properties like rheology, free water separation, fluid loss and compressive strength of slurries with and without polymer have been determined at 90 °C. The experimental results showed that the viscosity of HPMC polymer was enhanced at 90 °C than other cellulose-based polymers. The comparative and experimental analyses showed that the implementation of cellulose-based polymers improves the API properties of cement slurry at 90 °C. The increased viscosity of these polymers showed high rheology that was adjusted by adding dispersant which optimizes the rheology of slurry. Further, improved API properties, i.e., zero free water separation, none sedimentation, less than 50 ml/30 min fluid loss and high compressive strength, were obtained through HEC, CMC and HPMC polymer. It is concluded that cellulose-based polymers are efficient and effective in cement slurry that work as multifunctional additive and improve API properties and cement durability. The cellulose-based polymers work as multifunctional additive that reduces the quantity of other additives in cement slurry and ultimately reduces the operational cost of cementing operation. The comparative analysis of this study opens the window for petroleum industry for proper selection of cellulose-based polymer in designing of cement slurry.
Artificial neural network model for predicting the density of oil-based muds in high-temperature, high-pressure wells
Authors: Agwu Okorie E. , Akpabio Julius U. , Dosunmu Adewale
Published: November 2019

In this paper, an artificial neural network model was developed to predict the downhole density of oil-based muds under high-temperature, high-pressure conditions. Six performance metrics, namely goodness of fit (R2), mean square error (MSE), mean absolute error (MAE), mean absolute percentage error (MAPE), sum of squares error (SSE) and root mean square error (RMSE), were used to assess the performance of the developed model. From the results, the model had an overall MSE of 0.000477 with an MAE of 0.017 and an R2 of 0.9999, MAPE of 0.127, RMSE of 0.022 and SSE of 0.056. All the model predictions were in excellent agreement with the measured results. Consequently, in assessing the generalization capability of the developed model for the oil-based mud, a new set of data that was not part of the training process of the model comprising 34 data points was used. In this regard, the model was able to predict 99% of the unfamiliar data with an MSE of 0.0159, MAE of 0.101, RMSE of 0.126, SSE of 0.54 and a MAPE of 0.7. In comparison with existing models, the ANN model developed in this study performed better. The sensitivity analysis performed shows that the initial mud density has the greatest impact on the final mud density downhole. This unique modelling technique and the model it evolved represents a huge step in the trajectory of achieving full automation of downhole mud density estimation. Furthermore, this method eliminates the need for surface measurement equipment, while at the same time, representing more accurately the downhole mud density at any given pressure and temperature.
Bivariate exponentiated discrete Weibull distribution: statistical properties, estimation, simulation and applications
Authors: El- Morshedy M. , Eliwa M. S. , El-Gohary A. , Khalil A. A.
Published: November 2019

In this paper, a new bivariate discrete distribution is defined and studied in-detail, in the so-called the bivariate exponentiated discrete Weibull distribution. Several of its statistical properties including the joint cumulative distribution function, joint probability mass function, joint hazard rate function, joint moment generating function, mathematical expectation and reliability function for stress–strength model are derived. Its marginals are exponentiated discrete Weibull distributions. Hence, these marginals can be used to analyze the hazard rates in the discrete cases. The model parameters are estimated using the maximum likelihood method. Simulation study is performed to discuss the bias and mean square error of the estimators. Finally, two real data sets are analyzed to illustrate the flexibility of the proposed model.
You Are Only as Frail as Your Arteries: Prehabilitation of Elderly Surgical Patients
Authors: Durand Matthew J. , Beckert Angela K. , Peterson Carrie Y. , Ludwig Kirk A. , Ridolfi Timothy J. , Lauer Kathryn K. , Freed Julie K.
Published: November 2019

Purpose of Review

To discuss the concept of prehabilitation for the elderly frail surgical patient as well as strategies to improve preoperative functional capacity and vascular function to decrease postoperative complications.

Recent Findings

Frailty is associated with poor surgical outcomes yet there is no consensus on how frailty should be measured or mitigated in the preoperative period. Prehabilitation, or improving functional capacity prior to surgery typically through exercise, has been shown to be an effective strategy to decrease preoperative frailty and improves surgical outcomes. Use of remote ischemic preconditioning (RIPC) may serve as an alternative to exercise in this fragile patient population.

Prehabilitation programs using strategies targeted at improving vascular function may decrease frailty in the preoperative period and improve surgical outcomes in the elderly population.
Recent Progress and Approaches on Carbon-Free Energy from Water Splitting
Authors: Hossain Aslam , Sakthipandi K. , Atique Ullah A. K. M. , Roy Sanjay
Published: November 2019

Sunlight is the most abundant renewable energy resource, providing the earth with enough power that is capable of taking care of all of humanity’s desires—a hundred times over. However, as it is at times diffuse and intermittent, it raises issues concerning how best to reap this energy and store it for times when the Sun is not shining. With increasing population in the world and modern economic development, there will be an additional increase in energy demand. Devices that use daylight to separate water into individual chemical elements may well be the answer to this issue, as water splitting produces an ideal fuel. If such devices that generate fuel were to become widely adopted, they must be low in cost, both for supplying and operation. Therefore, it is essential to research for cheap technologies for water ripping. This review summarizes the progress made toward such development, the open challenges existing, and the approaches undertaken to generate carbon-free energy through water splitting.
Concerted Pair Motion Due to Double Hydrogen Bonding: The Formic Acid Dimer Case
Authors: Nejad Arman , Suhm Martin A.
Published: November 2019

Formic acid dimer as the prototypical doubly hydrogen-bonded gas-phase species is discussed from the perspective of the three translational and the three rotational degrees of freedom which are lost when two formic acid molecules form a stable complex. The experimental characterisation of these strongly hindered translations and rotations is reviewed, as are attempts to describe the associated fundamental vibrations, their combinations, and their thermal shifts by different electronic structure calculations and vibrational models. A remarkable match is confirmed for the combination of a CCSD(T)-level harmonic treatment and an MP2-level anharmonic VPT2 correction. Qualitatively correct thermal shifts of the vibrational spectra can be obtained from classical molecular dynamics in CCSD(T)-quality force fields. A detailed analysis suggests that this agreement between experiment and composite theoretical treatment is not strongly affected by fortuitous error cancellation but fully converged variational treatments of the six pair or intermolecular modes and their overtones and combinations in this model system would be welcome.
The learning hospital: From theory to practice in a hospital infection prevention program
Authors: Hess Olivia C.R. , Srivastava Meha , Pryor Rachel , Patrick Amie , Cooper Kaila , Godbout Emily , Anderson Katie , Doll Michelle , Stevens Michael P. , Hemphill Robin , Edmond Michael , Wenzel Richard , Bearman Gonzalo
Published: November 2019

The learning hospital is distinguished by ceaseless evolution of erudition, enhancement, and implementation of clinical best practices. We describe a model for the learning hospital within the framework of a hospital infection prevention program and argue that a critical assessment of safety practices is possible without significant grant funding. We reviewed 121 peer-reviewed manuscripts published by the VCU Hospital Infection Prevention Program over 16 years. Publications included quasi-experimental studies, observational studies, surveys, interrupted time series analyses, and editorials. We summarized the articles based on their infection prevention focus, and we provide a brief summary of the findings. We also summarized the involvement of nonfaculty learners in these manuscripts as well as the contributions of grant funding. Despite the absence of significant grant funding, infection prevention programs can critically assess safety strategies under the learning hospital framework by leveraging a diverse collaboration of motivated nonfaculty learners. This model is a valuable adjunct to traditional grant-funded efforts in infection prevention science and is part of a successful horizontal infection control program.
Adapt retrieval rules and inhibit already-existing world knowledge: adjustment of world knowledge’s activation level in auditory sentence comprehension
Authors: LI QIANYU , CHEN XUQIAN , SU QIAONING , LIU SHUN , HUANG JIAN
Published: November 2019

abstract

We tested whether the proportion of typical sentences in a series of auditory sentences would lead people to adjust the strength of activation of world knowledge (i.e., retrieval rules adaptation) during comprehension. This issue is important because it could help clarify how people efficiently integrate different memory information in cognitive processes. In two experiments, all task materials were presented to participants as a whole package, in which proportions of typical sentences, with typical final locations, varied under different conditions. In Experiment 1, the proportion of typical sentences was equal to the atypical ones (i.e., 50% typical vs. 50% atypical), whereas in Experiment 2, the proportion of typical sentences was not equal to the atypical ones (i.e., 75% typical vs. 25% atypical, and 25% typical vs. 75% atypical). Visual fixation on the critical area in a visual display before/while hearing the critical words was compared across conditions, and across-condition differences were used as an index of the adaptation of the retrieval rule in the activation of world knowledge. The findings indicated that the adaptation of retrieval rules occurs throughout the whole test package of sentence comprehension, and the strength of activation of world knowledge in sentence comprehension can be adjusted.
Effects of IDO1 and TDO2 inhibition on cognitive deficits and anxiety following LPS-induced neuroinflammation
Authors: Imbeault Sophie , Goiny Michel , Liu Xicong , Erhardt Sophie
Published: November 2019

Objective:

Sustained immune activation leads to cognitive dysfunctions, depression-, and anxiety-like behaviours in humans and rodents. It is modelled by administration of lipopolysaccharides (LPS) to induce expression of pro-inflammatory cytokines that then activate indoleamine 2,3 dioxygenase (IDO1), the rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. Here, we ask whether chronic IDO1 inhibition by 1-methyl-tryptophan (1-MT, added at 2 g/l in the drinking water) or chronic inhibition of tryptophan 2,3 dioxygenase (TDO2), another enzyme capable of converting tryptophan to kynurenine, by 680C91 (15 mg/kgper os), can rescue LPS-induced (0.83-mg/kg intraperitoneally) anxiety and cognitive deficits. We also investigate the acute effects of 680C91 on serotonergic, dopaminergic, and kynurenine pathway metabolites.

Methods:

We examined LPS-induced deficits in trace fear conditioning and anxiety in the light–dark box and elevated plus maze (EPM) in group-housed C57Bl6/N mice. Kynurenine pathway metabolites and monoamine levels were measured via high-performance liquid chromatography.

Results:

Chronic blockade of IDO1 with 1-MT did not rescue cognitive deficits or abrogate the anxiogenic behaviour caused by LPS despite a decrease in the brain kynurenine:tryptophan ratio. However, 1-MT by itself demonstrated anxiolytic properties in the EPM. Acute and chronic inhibition of TDO2 elevated brain levels of tryptophan, while chronic inhibition of TDO2 was unsuccessful in rescuing cognitive deficits and abrogating the anxiety caused by LPS.

Conclusions:

In line with previous studies, we show that LPS administration induces anxiety and cognitive dysfunctions in mice that however were not reversed by chronic blockade of IDO1 or TDO2 at the doses used.
Characterisation and outcome of neuropsychiatric symptoms in patients with anti-NMDAR encephalitis
Authors: Restrepo-Martinez Miguel , Ramirez-Bermudez Jesus , Bayliss Leo , Espinola-Nadurille Mariana
Published: November 2019

Background:

Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms.

Objective:

To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE.

Methods:

This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale.

Results:

24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259).

Conclusions:

Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.
In major depression, increased kappa and mu opioid receptor levels are associated with immune activation
Authors: Al-Hakeim Hussein Kadhem , Zeki Al-Fadhel Suhaer , Al-Dujaili Arafat Hussein , Maes Michael
Published: November 2019

Objective:

This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin – mu opioid receptor (MOR) and immune-inflammatory system.

Methods:

The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males.

Results:

Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence.

Conclusion:

Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress.
A RAMSEY TYPE RESULT FOR LATIN SQUARES
Authors: ZELENYUK YEVHEN , ZELENYUK YULIYA
Published: November 2019

We show that for all $m,k,r\in \mathbb{N}$, there is an $n\in \mathbb{N}$ such that whenever $L$ is a Latin square of order $m$ and the Cartesian product $L^{n}$ of $n$ copies of $L$ is $r$-coloured, there is a monochrome Latin subsquare of $L^{n}$, isotopic to $L^{k}$. In particular, for every prime $p$ and for all $k,r\in \mathbb{N}$, there is an $n\in \mathbb{N}$ such that whenever the multiplication table $L({\mathbb{Z}_{p}}^{n})$ of the group ${\mathbb{Z}_{p}}^{n}$ is $r$-coloured, there is a monochrome Latin subsquare of order $p^{k}$. On the other hand, we show that for every group $G$ of order $\leq 15$, there is a 2-colouring of $L(G)$ without a nontrivial monochrome Latin subsquare.
REPRESENTATION OF I(1) AND I(2) AUTOREGRESSIVE HILBERTIAN PROCESSES
Authors: Beare Brendan K. , Seo Won-Ki
Published: November 2019

We develop versions of the Granger–Johansen representation theorems for I(1) and I(2) vector autoregressive processes that apply to processes taking values in an arbitrary complex separable Hilbert space. This more general setting is of central relevance for statistical applications involving functional time series. An I(1) or I(2) solution to an autoregressive law of motion is obtained when the inverse of the autoregressive operator pencil has a pole of first or second order at one. We obtain a range of necessary and sufficient conditions for such a pole to be of first or second order. Cointegrating and attractor subspaces are characterized in terms of the behavior of the autoregressive operator pencil in a neighborhood of one.