bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimum sample size for developing a multivariable prediction model: PART II ‐ binary and time‐to‐event outcomes
Authors: Riley Richard D , Snell Kym IE , Ensor Joie , Burke Danielle L , Harrell Jr Frank E , Moons Karel GM , Collins Gary S
Published: October 2018

When designing a study to develop a new prediction model with binary or time‐to‐event outcomes, researchers should ensure their sample size is adequate in terms of the number of participants (n) and outcome events (E) relative to the number of predictor parameters (p) considered for inclusion. We propose that the minimum values ofnandE(and subsequently the minimum number of events per predictor parameter, EPP) should be calculated to meet the following three criteria: (i) small optimism in predictor effect estimates as defined by a global shrinkage factor of≥0.9, (ii) small absolute difference of≤0.05 in the model's apparent and adjusted Nagelkerke'sR2, and (iii) precise estimation of the overall risk in the population. Criteria (i) and (ii) aim to reduce overfitting conditional on a chosenp, and require prespecification of the model's anticipated Cox‐SnellR2, which we show can be obtained from previous studies. The values ofnandEthat meet all three criteria provides the minimum sample size required for model development. Upon application of our approach, a new diagnostic model for Chagas disease requires an EPP of at least 4.8 and a new prognostic model for recurrent venous thromboembolism requires an EPP of at least 23. This reinforces why rules of thumb (eg, 10 EPP) should be avoided. Researchers might additionally ensure the sample size gives precise estimates of key predictor effects; this is especially important when key categorical predictors have few events in some categories, as this may substantially increase the numbers required.
Design and other methodological considerations for the construction of human fetal and neonatal size and growth charts
Authors: Ohuma Eric O. , Altman Douglas G. ,   for the International Fetal and Newborn Growth Consortium for the 21 Century (INTERGROWTH-21 Project)
Published: October 2018

This paper discusses the features of study design and methodological considerations for constructing reference centile charts for attained size, growth, and velocity charts with a focus on human growth charts used during pregnancy. Recent systematic reviews of pregnancy dating, fetal size, and newborn size charts showed that many studies aimed at constructing charts are still conducted poorly. Important design features such as inclusion and exclusion criteria, ultrasound quality control measures, sample size determination, anthropometric evaluation, gestational age estimation, assessment of outliers, and chart presentation are seldom well addressed, considered, or reported. Many of these charts are in clinical use today and directly affect the identification of at‐risk newborns that require treatment and nutritional strategies.

This paper therefore reiterates some of the concepts previously identified as important for growth studies, focusing on considerations and concepts related to study design, sample size, and methodological considerations with an aim of obtaining valid reference or standard centile charts. We discuss some of the key issues and provide more details and practical examples based on our experiences from the INTERGROWTH‐21st Project. We discuss the statistical methodology and analyses for cross‐sectional studies and longitudinal studies in a separate article in this issue.
Moving beyond the conventional stratified analysis to estimate an overall treatment efficacy with the data from a comparative randomized clinical study
Authors: Tian L. , Jiang F. , Hasegawa T. , Uno H. , Pfeffer M. , Wei LJ.
Published: October 2018

For a two‐group comparative study, a stratified inference procedure is routinely used to estimate an overall group contrast to increase the precision of the simple two‐sample estimator. Unfortunately, most commonly used methods including the Cochran‐Mantel‐Haenszel statistic for a binary outcome and the stratified Cox procedure for the event time endpoint do not serve this purpose well. In fact, these procedures may be worse than their two‐sample counterparts even when the observed treatment allocations are imbalanced across strata. Various procedures beyond the conventional stratified methods have been proposed to increase the precision of estimation when the naive estimator is consistent. In this paper, we are interested in the case when the treatment allocation proportions vary markedly across strata. We study the stochastic properties of the two‐sample naive estimator conditional on the ancillary statistics, the observed treatment allocation proportions and/or the stratum sizes, and present a biased‐adjusted estimator. This adjusted estimator is asymptotically equivalent to the augmentation estimators proposed under the unconditional setting. Moreover, this consistent estimation procedure is also equivalent to a rather simple procedure, which estimates the mean response of each treatment group first via a stratum‐size weighted average and then constructs the group contrast estimate. This simple procedure is flexible and readily applicable to any target patient population by choosing appropriate stratum weights. All the proposals are illustrated with the data from a cardiovascular clinical trial, whose treatment allocations are imbalanced.
Synthesis of New Derivatives of 1,2,3‐Triazole‐Linked Phthalazine‐1,4‐dione in Water: Experimental Aspects and Molecular Docking Calculations
Authors: Bakherad Mohammad , Karami Saeed , Keivanloo Ali , Sepehri Saghi
Published: October 2018

A new series of phthalazine‐based 1,2,3‐triazole derivatives are synthesized by the reaction of 2‐methyl‐3‐(prop‐2‐yn‐1‐yl)‐2,3‐dihydro‐phthalazine‐1,4‐dione or 2,3‐bis(prop‐2‐yn‐1‐yl)‐2,3‐dihydrophthalaz‐ine‐1,4‐dione with aromatic azides via copper‐catalyzed azide‐alkyne cycloaddition reactions in the presence of metformine as a ligand. These reaction procedures have the advantages of high‐to‐excellent yields, short reaction times, mild experimental conditions, and operational simplicity. All the synthesized compounds are screened in vitro for their anti‐bacterial activities against the three bacterial strains Micrococcus luteus, Pseudomonas aeruginosa, and Bacillus subtilis. Furthermore, the results of anti‐bacterial activity of the synthesized compounds was investigated using molecular docking calculations.
Synthesis and Studies of New Fluorescein‐Porphyrin Dyads: A Theoretical and Experimental Approach
Authors: Rezazgui Olivier , Marchand Guillaume , Trouillas Patrick , Siegler Benjamin , Leroy‐Lhez Stéphanie
Published: October 2018

Synthesis of two new zinc porphyrin fluorescein dyads are reported here. The two chromophoric units are covalently linked by alkane or alkyne bond, which provides various degrees of flexibility. Conformational analysis as photophysical properties were performed both experimentally (NOESY experiments, lifetimes, ROS production…) and theoretically (DFT and TD‐DFT calculations). Comparison with triazole linker described in a precedent study highlighted that linkage nature determine conformational structure (folding/linearity) but do not significantly modify energy transfer between the two moieties involved in dyads.
Supramolecular Architectures of Polyoxometalate Hybrids Originating from Halogen and Hydrogen‐Bonding Interactions
Authors: Lin Xinjun , Huang Bo , Xiong Zhelun , Fang Ting , Zhang Xiaoxiao , Xiao Zicheng , Wu Pingfan
Published: October 2018

In this paper, we explored the possibility of building halogen bonds between polyoxometalate anions by synthesizing a series of polyoxometalate clusters covalently linked to different halogen atoms. Among these samples, the polyoxometalate hybrids containing bromide and iodine atoms exhibited both halogen and hydrogen bonding interactions between the hybrid anions, leading to novel 3D framework assemblies.
Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts
Authors: Zheng Mengjia , Wiraja Christian , Yeo David C. , Chang Hao , Lio Daniel Chin Shiuan , Shi Wei , Pu Kanyi , Paller Amy S. , Xu Chenjie
Published: October 2018

Early diagnosis and timely intervention are key for the successful treatment of skin diseases like abnormal scars. This study introduces a nucleic‐acid‐based probe (i.e., molecular sprinkler) for the diagnosis and spontaneous regulation of the abnormal expression of fibrosis‐related mRNA in scar‐derived skin fibroblasts. Using mRNA encoding connective tissue growth factor (CTGF) as the model gene, a probe with three oligonucleotides is constructed, including a recognition sequence complementary to the CTGF mRNA, a siRNA against transforming growth factor receptor I (TGFβRI) as the CTGF mRNA suppressor, and a connecting sequence. The probe can detect CTGF mRNA with a limit of 10 × 10−9
m and distinguishes scar fibroblasts from normal ones in both 2D and 3D environments. Two days after transfection, the siRNA released from the probe reduces the expression of TGFβRI and, consequently, decreases the cellular expression of CTGF mRNA (up to 70%). This dual‐role probe presents opportunities to monitor the TGF‐ β signaling pathway, screen for drugs that target the CTGF pathway, and determine the role of inhibition of the CTGF pathway in therapeutic efficacy.
Tailoring the Properties of Native Andean Potato Starch Nanoparticles Using Acid and Alkaline Treatments
Authors: Torres Fernando G. , Arroyo Junior , Tineo Carlos , Troncoso Omar
Published: October 2018

Starch is among the biopolymers that have been successfully used to extract nanoparticles through a variety of processing routes. Most of these processes require chemical or mechanical‐physical treatments that erode and break down the starch granules into nanoparticles. We have evaluated the use of four treatments for the production of starch‐based nanoparticles from three varieties of native Andean potatoes. These treatments include either an acid or alkaline hydrolysis stage to disrupt the starch granules’ structure. We have assessed the morphology and size of these nanoparticles. It is found that, in the case of acid‐based treatments, the size of the nanoparticles is dependent on the variety of potato used. In the case of the alkali‐based treatments, the sizes obtained are statistically independent of the variety of potato used. In addition, the acid‐based treatments are found to preserve the crystalline structure of the variety of starch used whereas the alkali‐based treatments destroy the starch granules and change the crystalline structure of the starch. Different processing routes can be used to customize the specific properties of starch nanoparticles. The results suggest that native starch sources can be used to obtain starch nanoparticles with tailor‐made properties.
Poly(ADP-Ribose) Polymerase Inhibition Sensitizes Colorectal Cancer-Initiating Cells to Chemotherapy
Authors: Jarrar Awad , Lotti Fiorenza , DeVecchio Jennifer , Ferrandon Sylvain , Gantt Gerald , Mace Adam , Karagkounis Georgios , Orloff Matthew , Venere Monica , Hitomi Masahiro , Lathia Justin , Rich Jeremy N. , Kalady Matthew F.
Published: October 2018

Colorectal cancer (CRC) remains a leading killer in the U.S. with resistance to treatment as the largest hurdle to cure. Colorectal cancer-initiating cells (CICs) are a self-renewing tumor population that contribute to tumor relapse. Here, we report that patient-derived CICs display relative chemoresistance compared with differentiated progeny. In contrast, conventional cell lines failed model therapeutic resistance. CICs preferentially repaired chemotherapy-induced DNA breaks, prompting us to interrogate DNA damage pathways against which pharmacologic inhibitors have been developed. We found that CICs critically depended on the key single-strand break repair mediator, poly(ADP-ribose) polymerase (PARP), to survive treatment with standard-of-care chemotherapy. Small molecule PARP inhibitors (PARPi) sensitized CICs to chemotherapy and reduced chemotherapy-treated CIC viability, self-renewal, and DNA damage repair. Although PARPi monotherapy failed to kill CICs, combined PARPi therapy with chemotherapy attenuated tumor growth in vivo. Clinical significance of PARPi for CRC patients was supported by elevated PARP levels in colorectal tumors compared with normal colon, with further increases in metastases. Collectively, our results suggest that PARP inhibition serves as a point of fragility for CICs by augmenting therapeutic efficacy of chemotherapy. Stem Cells  2019;37:42–53
Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma
Authors: Coffman Lan G. , Pearson Alexander T. , Frisbie Leonard G. , Freeman Zachary , Christie Elizabeth , Bowtell David D. , Buckanovich Ronald J.
Published: October 2018

Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment (TME). We previously demonstrated that CA-MSCs differentially express bone morphogenetic protein family members, promote tumor cell growth, increase cancer “stemness,” and chemotherapy resistance. Here, we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate global changes in CA-MSC gene expression. Using these expression profiles, we create a unique predictive algorithm to classify CA-MSCs. Our classifier accurately distinguishes normal omental, ovary, and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. Although cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian TME can reprogram omental or ovary MSCs to protumorigenic CA-MSCs (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, although the breast cancer TME can reprogram bone marrow MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (a) provide a critical tool to define CA-MSCs and (b) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Stem Cells  2019;37:257–269
Effects of Hydrology on Fish Diversity and Assemblage Structure in a Texan Coastal Plains River
Authors: Bower Luke M. , Keppeler Friedrich W. , Cunha Eduardo R. , Quintana Yasmin , Saenz David E. , Lopez‐Delgado Edwin O. , Bokhutlo Thethela , Arantes Caroline C. , Andrade Marcelo C. , Robertson Clinton R. , Mayes Kevin B. , Winemiller Kirk O.
Published: October 2018

High‐flow pulses affect river ecosystem dynamics in many important ways including by forming connections between the channel and oxbow lakes. This study assessed the influence of discharge on fish assemblage structure and diversity in the channel and oxbows of the Guadalupe River, Texas. Local assemblages of two oxbows and two channel sites were surveyed using standardized methods to test four hypotheses: (1) assemblage structure in oxbow lakes differs from those in the river channel, (2) α diversity decreases during extended periods of low discharge, (3) β diversity decreases during high discharge and increases during extended periods of low discharge, and (4) species turnover and assemblage nestedness decline during periods of high discharge. We found evidence to support the first three hypotheses. Unsurprisingly, lotic‐adapted fishes were observed more frequently in the river channel, whereas lentic‐adapted species generally were more common in the oxbow lakes. Species richness declined during periods of low discharge possibly due to harsher environmental conditions or stronger species interactions (e.g., predation). Discharge was inversely associated with both β diversity and species turnover, suggesting a stronger mass effect during high‐flow pulses, and stronger species sorting during low‐flow conditions. Contrary to our fourth hypothesis, assemblage nestedness increased during periods of high discharge. Finally, we also found evidence to support the hypothesis that species turnover decreased as discharge declined. The results of this study demonstrate the importance of flow pulses for maintaining fish diversity and assemblage structure in floodplain river systems. With additional research involving more sites and longer time series, it should be feasible to define and identify thresholds for flow regime changes that alter assemblage structure and species diversity.
How a Third‐Grade Reading Retention Law Will Affect ELLs in Michigan, and a Call for Research on Child ELL Reading Development
Authors: Winke Paula , Zhang Xiaowan
Published: October 2018

Video Abstract
Microstructural studies of composite Mughal period cannons of Daulatabad Fort, India, by electron backscattered diffraction and scanning electron microscopy
Authors: Singh Manager Rajdeo
Published: October 2018

Historical data on ancient Indian cannons have systematically been researched, but there is lack of archaeometallurgical studies on bimetallic cannons. This study revolves around 16th–17th century bimetallic Indian cannons: copper barrel with inner iron sleeve at an approximate ratio of 5:1. Scanning electron microscopy and electron backscattered diffraction techniques have been employed to know the changes in the microstructures of the metals used in making cannons. Energy dispersive spectrometry confirmed that the outer copper barrel, with 4.5 wt% tin, had inclusions of cupric oxide (Cu2O) and contained lead and sulfur. The inner sleeve, on the other hand, was primarily iron but contained fayalite (FeSiO4) and inclusions with silicon and phosphorous. Both inner (bloomery iron) and outer (copper) material had strong signatures of plastic deformation, and the cannons were stipulated to be forge welded. Deformation twinning in recrystallized iron grains of inner iron sleeve and near‐perfect extensive twinning in the inner copper barrel indicate exposures of the respective materials to such active usage. It is concluded from the deformed structures and from the presence of clear joints that the bimetallic cannons were made by a process of forge welding. This study brings actual manufacturing practices of bimetallic cannons in ancient India.
A quantum hydrodynamical description for scrambling and many-body chaos
Authors: Blake Mike , Lee Hyunseok , Liu Hong
Published: October 2018

Abstract

Recent studies of out-of-time ordered thermal correlation functions (OTOC) in holographic systems and in solvable models such as the Sachdev-Ye-Kitaev (SYK) model have yielded new insights into manifestations of many-body chaos. So far the chaotic behavior has been obtained through explicit calculations in specific models. In this paper we propose a unified description of the exponential growth and ballistic butterfly spreading of OTOCs across different systems using a newly formulated “quantum hydrodynamics,” which is valid at finite ℏ and to all orders in derivatives. The scrambling of a generic few-body operator in a chaotic system is described as building up a “hydrodynamic cloud,” and the exponential growth of the cloud arises from a shift symmetry of the hydrodynamic action. The shift symmetry also shields correlation functions of the energy density and flux, and time ordered correlation functions of generic operators from exponential growth, while leads to chaotic behavior in OTOCs. The theory also predicts an interesting phenomenon of the skipping of a pole at special values of complex frequency and momentum in two-point functions of energy density and flux. This pole-skipping phenomenon may be considered as a “smoking gun” for the hydrodynamic origin of the chaotic mode. We also discuss the possibility that such a hydrodynamic description could be a hallmark of maximally chaotic systems.
Rindler-AdS/CFT
Authors: Parikh Maulik , Samantray Prasant
Published: October 2018

Abstract

In anti-de Sitter space a highly accelerating observer perceives a Rindler horizon. The two Rindler wedges in AdS

d+1 are holographically dual to an entangled conformal field theory that lives on two boundaries with geometry ℝ × H

d−1. For AdS3, the holographic duality is especially tractable, allowing quantum-gravitational aspects of Rindler horizons to be probed. We recover the thermodynamics of Rindler-AdS space directly from the boundary conformal field theory. We derive the temperature from the two-point function and obtain the Rindler entropy density precisely, including numerical factors, using the Cardy formula. We also probe the causal structure of the spacetime, and find from the behavior of the one-point function that the CFT “knows” when a source has fallen across the Rindler horizon. This is so even though, from the bulk point of view, there are no local signifiers of the presence of the horizon. Finally, we discuss an alternate foliation of Rindler-AdS which is dual to a CFT living in de Sitter space.
Focus point gauge mediation without a severe fine-tuning
Authors: Yanagida Tsutomu T. , Yokozaki Norimi
Published: October 2018

Abstract

We consider focus point gauge mediation within the framework of the next-to-minimal supersymmetric standard model, which substantially reduces the degree of finetuning for the electroweak symmetry breaking. The milder fine-tuning is realized by a messenger field in the adjoint representation of SU(5) gauge group with SU(3)
c
octet being heavy. Our model has a simple ultraviolet completion. The fine-tuning measure Δ can be as small as 40-50 without any contradiction with LHC constraints.
Vocal Cord Palsies Missed by Transcutaneous Laryngeal Ultrasound (TLUSG): Do They Experience Worse Outcomes?
Authors: Wong Kai‐Pun , Au Kin Pan , Lam Shi , Chang Yuk Kwan , Lang Brian Hung Hin
Published: October 2018

Introduction

Transcutaneous laryngeal ultrasound (TLUSG) is an innovative, non‐invasive tool in detecting post‐thyroidectomy vocal cord palsy (VCP). However, TLUSG failed to detect about 6–15% laryngoscopic examination (LE)‐confirmed VCP. It is unclear whether the outcome of patients with VCP missed by TLUSG [false negative (FN)] is different from those with VCP diagnosed by TLUSG [true positive (TP)]. Therefore, this study aimed to compare the clinical outcome and prognosis between patients with FN results and TP results.

Methods

Over 46 months, all consecutive patients undergoing thyroidectomy or endocrine‐related neck procedure were recruited. They underwent pre‐operative and post‐operative voice assessments on symptoms, voice‐specific questionnaire [voice handicap index questionnaire (VHI‐30)], TLUSG and LE. For patients with post‐operative vocal cord palsy, reassessment LE would be arranged at second, fourth, sixth and twelfth months post‐operatively until VCP recovered.

Results

In total, 1196 patients, including 74 post‐thyroidectomy VCP, were recruited. For those with assessable vocal cords (VC), 58 VCP were correctly diagnosed by TLUSG (TP) and 10 VCP were missed by TLUSG (FN). Sensitivity and specificity of detecting a VCP by TLUSG were 85.3% and 94.7%, respectively. VHI‐30 score was significantly increased after operation in TP group [31 (range − 6–105), p < 0.001] but not in FN group [20 (14–99), p = 0.089]. Comparing to TP group, VCP recovered earlier (69 vs. 125 days, p < 0.001) and less patients suffered from permanent VCP in patients with FN results. (34.5% vs. 0.0%, p = 0.027).

Conclusion

The VCP missed by TLUSG had a milder course of disease. Early recovery of VC function and non‐permanent palsy were expected.
How Pornography Use Reduces Participation in Congregational Leadership: A Research Note
Authors: Perry Samuel L.
Published: October 2018

Research on the link between religion and pornography suggests that more frequent pornography viewing can lead to declines in individuals’ religious commitment, likely stemming from the guilt, shame, and dissonance adherents experience for violating sacralized moral values. No research, however, has considered the implications of this phenomenon for religious organizations. The current study addresses this gap by examining how pornography use contributes to potential congregational problems by discouraging individuals from participating in lay leadership. Multivariate analyses of panel data from the 2006–2012 Portraits of American Life Study reveal that the more frequently respondents viewed pornography at wave 1 the less likely they were to hold a leadership position or serve on a committee in their congregation within the following 6 years. This effect was robust to controls for religious commitment, tradition, and other correlates of lay leadership participation. Interactions with religious tradition and gender suggest that participation in leadership is more negatively tied to porn use for conservative Protestants and Catholics compared to mainline Protestants and women compared to men. Findings ultimately suggest that increasingly pervasive pornography consumption among adherents could portend a potential dearth of volunteer leadership for congregations.
miR-137 Affects Vaginal Lubrication in Female Sexual Dysfunction by Targeting Aquaporin-2
Authors: Zhang Hepeng , Liu Tianjiao , Zhou Ziyun , Zhang Aixia , Zhu Yuan , Zhang Jing , Pan Lianjun , Ma Jiehua
Published: October 2018

Introduction

Female sexual dysfunction (FSD) is a common disease with serious potential hazards, but it has not received much attention. The pathogenesis of FSD is urgently needed for the diagnosis and treatment of FSD.

Aim

To investigate the role of microribonucleic acid (mRNA, miR)-137 in FSD.

Methods

Vaginal epithelium tissues from 15 women with lubrication disorder and 15 women with normal function were collected for this study. The expression level of miR-137 in lubrication disorder and normal function women were measured by microarray analysis and Real-time Quantitative Polymerase Chain Reaction (PCR, qPCR). miR-137 was overexpressed in vaginal epithelial cells VK2/E6E7 by lentivirus infection. The cell water permeability was measured using the calcein-quenching method. Cell apoptosis was analyzed by flow cytometry. The potential target of miR-137 was predicted by bioinformatic analysis, then verified by luciferase reporter assays.

Main Outcome Measure

The expression level of miR-137 and aquaporin-2 (AQP2), cell water permeability, cell apoptosis, and luciferase reporter assays were examined.

Results

miR-137 was found to be highly expressed in vaginal epithelial tissues of women with lubrication disorder. Additionally, functional in vitro studies suggested that overexpression of miR-137 leads to a decrease in cell permeability. By combining target prediction and examination, we identified AQP2 as the direct mechanistic target of miR-137 that affected the water permeability of vaginal epithelial cells.

Conclusion

Our results point to a novel role for miR-137 and its downstream effector AQP2 in vaginal lubrication, which can be manipulated as therapeutic targets against lubrication disorder and its related disorders.
Kant on Civil Society and Welfare
Authors: Holtman Sarah
Published: October 2018

What justifies state-sponsored supports for individual welfare within a Kantian political system, as well as the purpose and extent of such supports and the form they may take, are vexed questions. This Element characterizes and assesses main contenders (including minimalist and middle-ground accounts) by examining the competing interpretations of Kant's larger political theory that found their social welfare claims. It then develops and defends an alternative based in civic respect. This emphasizes the perspective and institutional commitments Kant's model of citizenship entails and what is required to respect each as both a person and a participant in joint governance.
Acute effects of non-homogenised and homogenised vegetables added to rice-based meals on postprandial glycaemic responses and in vitro carbohydrate digestion
Authors: Zhu Ruixin , Liu Manman , Han Yue , Wang Linlin , Ye Ting , Lu Jiacan , Fan Zhihong
Published: October 2018

The addition of vegetable to carbohydrate-based meals was shown to contribute to glycaemic management. The aim of this study was to investigate the impact of homogenisation on vegetables added to rice meals in terms of acute glycaemic responses (GR). In a randomised crossover trial, sixteen healthy volunteers completed thirteen test sessions, which included two sessions for glucose control, two for rice and nine for different vegetable-rice mixed meals: cooked pak choi and cooked rice (CP+R); cooked cauliflower and cooked rice (CC+R); cooked eggplant and cooked rice (CE+R); and their homogenised counterparts, both raw or cooked. Postprandial GR tests, in vitro carbohydrate digestion and chemical analyses were carried out for each test meal. Compared with pure rice, CE+R, CP+R and CC+R meals achieved significantly lower glycaemic indexes (GI) of 67, 71 and 73, whereas their homogenised counterparts failed to show significant difference with rice. The hydrolysis indexes (HI) of CE+R, CP+R and CC+R were 69·6, 83·8 and 80·6 % of the HI of the rice control. CE had the greatest effect on lowering the GI, the incremental area under the blood glucose curve from 0 to 120 min, the peak glucose value, the maximum amplitude of glucose excursion in 0–120 min (MAGE0–120), the HI and rapid available starch. Both in vitro and in vivo tests demonstrated that incorporating non-homogenised cooked vegetables into a rice meal could slow the carbohydrate digestion and improve postprandial GR. Texture properties of vegetable may play an important role in underlying glycaemic control mechanisms.
Capital Asset Pricing with a Stochastic Horizon
Authors: Brennan Michael J. , Zhang Yuzhao
Published: October 2018

In this paper we present empirical tests of an extended version of the capital asset pricing model (CAPM) that replaces the single-period horizon with a probability distribution over different horizons. Adopting a simple parameterization of the probability distribution of the length of the horizon, we estimate the parameters of the distribution as well as the parameters of the CAPM. We find that the extended model is not rejected for several different samples of common stocks, and for these samples it outperforms not only the standard CAPM but also the Fama–French (1993) 3-factor model. The probability distribution over horizon dates varies over time with the New York Stock Exchange (NYSE) turnover rate. We also find that returns satisfy the Euler equation of a representative financial institution that holds the market portfolio and has horizon probabilities estimated from 13F filings.
Tinnitus information online – does it ring true?
Authors: McKearney R M , MacKinnon R C , Smith M , Baker R
Published: October 2018

Objective

To assess, using standardised tools, the quality and readability of online tinnitus information that patients are likely to access.

Methods

A standardised review was conducted of websites relating to tinnitus and its management. Each website was scored using the DISCERN instrument and the Flesch Reading Ease scale.

Results

Twenty-seven unique websites were evaluated. The mean DISCERN score of the websites was 34.5 out of 80 (standard deviation = 11.2). This would be considered ‘fair’ in quality. Variability in DISCERN score between websites was high (range, 15–57: ‘poor’ to ‘very good’). Website readability was poor, with a mean Flesch Reading Ease score of 52.6 (standard deviation = 7.7); this would be considered ‘difficult’ to read.

Conclusion

In general, the quality of tinnitus websites is fair and the readability is poor, with substantial variability in quality between websites. The Action on Hearing Loss and the British Tinnitus Association websites were identified as providing the highest quality information.
Neuromotor performance in infants before and after early open-heart surgery and risk factors for delayed development at 6 months of age
Authors: Campbell Miranda J. , Ziviani Jenny M. , Stocker Christian F. , Khan Asaduzzaman , Sakzewski Leanne
Published: October 2018

Background

Early identification of infants with CHD at heightened risk of developmental delays can inform surveillance priorities. This study investigated pre-operative and post-operative neuromotor performance in infants undergoing open-heart surgery, and their developmental status at 6 months of age, to identify risk factors and inform care pathways.

Methods

Infants undergoing open-heart surgery before 4 months of age were recruited into a prospective cohort study. Neuromotor performance was assessed pre-operatively and post-operatively using the Test of Infant Motor Performance and Prechtl’s Assessment of General Movements. Development was assessed at 6 months of age using the Ages and Stages Questionnaire third edition. Pre-operative and post-operative General Movements performance was compared using McNemar’s test and test of infant motor performance z-scores using Wilcoxon’s signed rank test. Risk factors for delayed development at 6 months were explored using logistic regression.

Results

Sixty infants were included in this study. In the 23 (38%) infants. A total of 60 infants were recruited. In the 23 (38%) infants assessed pre-operatively, there was no significant difference between pre- and post-operative performance on the GMs (p=0.63) or TIMP (p=0.28). At discharge, 15 (26%) infants presented with abnormal GMs, and the median TIMP z-score was −0.93 (IQR: −1.4 to −0.69). At 6 months, 28 (52.8%) infants presented with gross motor delay on the ASQ-3, significantly negatively associated with gestational age (p=0.03), length of hospital stay (p=0.04) and discharge TIMP score (p=0.01).

Conclusions

Post-operative assessment using the GMs and TIMP may be useful to identify infants requiring individualised care and targeted developmental follow-up. Long-term developmental surveillance beyond 6 months of age is recommended.
Decisional control preferences of patients with advanced cancer receiving palliative care
Authors: Tricou Colombe , Yennu Sriram , Ruer Murielle , Bruera Eduardo , Filbet Marilène
Published: October 2018

Objective:

Understanding patients' decisional control preferences (DCPs) is important to improving the quality of care and the satisfaction of patients who have advanced cancer with their care. In addition to passive decisional control (i.e., the patient prefers his/her doctor or family caregiver to make a decision on their behalf) and active decisional control (i.e., the patient decides alone), shared decisional control, where patients and caregivers decide together, could be more appropriate. The primary aim of our study was to describe the decision-making process and the DCPs of patients with advanced cancer receiving palliative care in France.

Method:

We conducted a prospective survey with advanced cancer patients referred to a palliative care team in an outpatient setting. We collected information about patients' demographic and clinical characteristics using the Decision Control Preference Scale, the Satisfaction with the Decisions and Care questionnaire, and the Understanding of Illness questionnaire.

Results:

A total of 200 patients were evaluable. The median age was 63.5 years and 53.5% female. The cancers most commonly represented were gastrointestinal and breast. A total of 72 patients (36.2%) preferred active decisional control, 52 (26.1%) preferred shared decisional control, and 75 (37.7%) preferred passive decisional control. Younger age (p = 0.003), higher education (p < 0.001), and employment status (p = 0.046) were found to be associated with active or shared DCPs. Some 82% of patients were satisfied with the decision-making process, 35% of whom expressed wishes that did not match the actual decision-making process. Only 23% of patients thought they could be cured of their illness, and 47% thought that their treatment would “get rid of ” their disease.

Significance of Results:

The decision-making processes are shared in the three models of DCPs in our cohort of French patients with advanced cancer. Further prospective studies are needed.
Beyond the 1984 Perspective: Narrow Focus on Modern Wildfire Trends Underestimates Future Risks to Water Security
Authors: Murphy Brendan P. , Yocom Larissa L. , Belmont Patrick
Published: October 2018

The western United States remains well below historical wildfire activity, yet misconceptions abound in the public and news media that the area burning by wildfire each year in the American West is unprecedented. We submit that short‐term records of wildfire and a disproportionate focus on recent fire trends within high‐profile science stoke these misconceptions. Furthermore, we highlight serious risks to long‐term water security (encompassing water supply, storage, and quality) that have only recently been recognized and are underestimated as the result of skewed perspectives of wildfire. Compiling several data sets, we illustrate a comprehensive history of western wildfire, demonstrate that the majority of western settlement occurred during an artificially and anomalously low period of wildfire in the twentieth century, and discuss the troubling implications the misalignment of wildfire activity and human development may have for the long‐term projections of water security. A crucial first step toward realigning public perspectives will require scientists and journalists to present recent increases in wildfire area within the context and scale of longer‐term trends. Second, proper housing development and resource management will require an appreciation for the differing western ecosystems and the flexibility to adopt varied approaches. These actions are critical for realigning public understanding of both the direct and indirect risks associated with wildfire and ensuring adequate and appropriate measures are taken as we navigate a future of increasing fire in the West.
Huge Blades of Ice May Partially Cover Jupiter’s Moon Europa
Authors: Kornei Katherine
Published: October 2018

Conditions are right for “penitentes” up to 15 meters high to form on the Jovian moon, new research shows. The spires might prevent a lander from exploring Europa’s equatorial region.
Microplastics Found in Human Stool
Authors: Duncombe Jenessa
Published: October 2018

Tiny slivers of plastic are making it all the way into humans’ guts and into their feces, a new study shows.
Diffusion Profiles Around Quartz Clasts as Indicators of the Thermal History of Pseudotachylytes
Authors: Dobson David P. , Thomas Richard W. , Mitchell Thomas M.
Published: October 2018

Pseudotachylytes are generated by the cooling and solidification of frictional melt produced along a fault surface during seismic slip. Pseudotachylytes can, therefore, provide important constraints on thermal histories of faults during coseismic slip: survivor clast mineralogies and quenched crystallite morphologies have previously been used to constrain the peak temperatures during slip. Here we show that silicon‐diffusion gradients are preserved around quartz survivor clasts and that these can be used to constrain the immediate cooling histories of pseudotachylytes after the cessation of slip. The variation of diffusion length with position in pseudotachylyte veins can be well reproduced by combining simple thermal history models with Arrhenius parameters for diffusion of appropriate magma compositions.
Global Cooling Contributed to the Establishment of a Modern‐Like East Asian Monsoon Climate by the Early Miocene
Authors: Zhang Ran , Zhang Zhongshi , Jiang Dabang
Published: October 2018

The establishment of a modern‐like monsoon climate in East Asia by the early Miocene was a complex process forced by several factors, and previous studies paid less attention to global cooling. Here we investigate this process using climate modeling by considering changes in topography and global cooling under the early Miocene boundary conditions. Using early Miocene paleogeography and an atmospheric CO2 concentration of 560 ppmv, our model results indicate that a nonzonal climate pattern has appeared in East China but that this climate exhibits weak precipitation and wind seasonality. Such seasonality strengthens as the concentration of atmospheric CO2 decreases from 560 to 420 ppmv and resembles the modern‐like condition after the growth of the Antarctic ice sheet. Although the development of East Asian topography can further strengthen this seasonality, our results indicate that global cooling is also pivotal for the establishment of a modern‐like monsoon climate in East Asia.
Improving the Reliability and Added Value of Dynamical Downscaling via Correction of Large‐Scale Errors: A Norwegian Perspective
Authors: Pontoppidan M. , Kolstad E.W. , Sobolowski S. , King M. P.
Published: October 2018

Heavy precipitation and associated flooding are major concerns for western Norway under both present climate conditions and projected future scenarios. In winter, these events are mostly caused by North Atlantic low‐pressure systems. However, the storm track in this region is systematically biased in most global climate models. Further, these models are unable to capture the interactions between synoptic systems and the complex topography due to their coarse resolution, which contributes to poor representation of precipitation. In this study we employed a correction technique to remove the mean biases from multiple variables in a global Earth system model (Norwegian Earth System Model), and we subsequently dynamically downscaled a 38‐year period. The effect of the bias correction was a more realistic storm track and an improved precipitation distribution in southern Norway. Our results indicate that it is possible to enhance the reliability of regional climate simulations with positive implications for regional climate projections and climate change impact studies.
Parametric Sensitivity and Uncertainty Quantification in the Version 1 of E3SM Atmosphere Model Based on Short Perturbed Parameter Ensemble Simulations
Authors: Qian Yun , Wan Hui , Yang Ben , Golaz Jean‐Christophe , Harrop Bryce , Hou Zhangshuan , Larson Vincent E. , Leung L. Ruby , Lin Guangxing , Lin Wuyin , Ma Po‐Lun , Ma Hsi‐Yen , Rasch Phil , Singh Balwinder , Wang Hailong , Xie Shaocheng , Zhang Kai
Published: October 2018

The atmospheric component of Energy Exascale Earth System Model version 1 has included many new features in the physics parameterizations compared to its predecessors. Potential complex nonlinear interactions among the new features create a significant challenge for understanding the model behaviors and parameter tuning. Using the one‐at‐a‐time method, the benefit of tuning one parameter may offset the benefit of tuning another parameter, or improvement in one target variable may lead to degradation in another target variable. To better understand the Energy Exascale Earth System Model version 1 model behaviors and physics, we conducted a large number of short simulations (three days) in which 18 parameters carefully selected from parameterizations of deep convection, shallow convection, and cloud macrophysics and microphysics were perturbed simultaneously using the Latin hypercube sampling method. From the perturbed parameter ensemble simulations and use of different skill score functions, we identified the most sensitive parameters, quantified how the model responds to changes of the parameters for both global mean and spatial distribution, and estimated the maximum likelihood of model parameter space for a number of important fidelity metrics. Comparison of the parametric sensitivity using simulations of two different lengths suggests that perturbed parameter ensemble using short simulations has some bearing on understanding parametric sensitivity of longer simulations. Results from this analysis provide a more comprehensive picture of the Energy Exascale Earth System Model version 1 behavior. The difficulty in reducing biases in multiple variables simultaneously highlights the need of characterizing model structural uncertainty (so‐called embedded errors) to inform future development efforts.
Snow Depth Variability at the Forest Edge in Multiple Climates in the Western United States
Authors: Currier William Ryan , Lundquist Jessica D.
Published: October 2018

Snow depth variability between different sides of the forest edge was analyzed using airborne lidar in the Olympic Mountains, WA; Tuolumne River Watershed, CA; Jemez Caldera, NM; and the Boulder Creek Watershed, CO. At Boulder Creek there were statistically significant snow depth differences between leeward and windward forest edges (mean: 38%), which were likely the result of cold winter temperatures (−5 to −10°C), substantial wind speeds (>10–12 m/s), and the forest architecture. In the Olympic Mountains, wind speeds were similar to Boulder Creek, but snow depth differences between forest edges were not significantly different, likely due to winter temperatures near 0°C and a more continuous forest distribution. At Jemez, forest shading likely caused significant snow depth differences between north and south facing forest edges (mean: 32%). Tuolumne had similar incoming solar radiation to Jemez, but only two of the four sites contained significant snow depth differences between north and south facing forest edges (14% and 31%). The Tuolumne sites without significant edge differences received less direct solar radiation due to shading by surrounding topography. At Jemez, Boulder Creek, and Tuolumne, snow depth differences between forest edges were greater than or equal to differences between exposed and under canopy areas. Furthermore, at Jemez and Tuolumne, forest‐edge snow depth differences were similar to snow depth differences between different aspects in exposed areas. Therefore, snow depth differences between forest‐edge classifications are of similar magnitude to classifications currently used to represent subelement heterogeneity within hydrologic models. Therefore, representation of forest‐edge variability within models should be explored.
T-LAK cell-originated protein kinase (TOPK): an emerging target for cancer-specific therapeutics
Authors: Herbert Katharine J. , Ashton Thomas M. , Prevo Remko , Pirovano Giacomo , Higgins Geoff S.
Published: October 2018

‘Targeted’ or ‘biological’ cancer treatments rely on differential gene expression between normal tissue and cancer, and genetic changes that render tumour cells especially sensitive to the agent being applied. Problems exist with the application of many agents as a result of damage to local tissues, tumour evolution and treatment resistance, or through systemic toxicity. Hence, there is a therapeutic need to uncover specific clinical targets which enhance the efficacy of cancer treatment whilst minimising the risk to healthy tissues. T-LAK cell-originated protein kinase (TOPK) is a MAPKK-like kinase which plays a role in cell cycle regulation and mitotic progression. As a consequence, TOPK expression is minimal in differentiated cells, although its overexpression is a pathophysiological feature of many tumours. Hence, TOPK has garnered interest as a cancer-specific biomarker and biochemical target with the potential to enhance cancer therapy whilst causing minimal harm to normal tissues. Small molecule inhibitors of TOPK have produced encouraging results as a stand-alone treatment in vitro and in vivo, and are expected to advance into clinical trials in the near future. In this review, we present the current literature pertaining to TOPK as a potential clinical target and describe the progress made in uncovering its role in tumour development. Firstly, we describe the functional role of TOPK as a pro-oncogenic kinase, followed by a discussion of its potential as a target for the treatment of cancers with high-TOPK expression. Next, we provide an overview of the current preclinical progress in TOPK inhibitor discovery and development, with respect to future adaptation for clinical use.