bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Intra‐Subject Variability of Reaction Times and Single‐Trial Event‐Related Potential Components in Children With Autism Spectrum Disorder
Authors: Magnuson Justine R. , Iarocci Grace , Doesburg Sam M. , Moreno Sylvain
Published: October 2019

Autism spectrum disorder (ASD) is an increasingly common neurodevelopmental disorder that affects 1 in 59 children. The cognitive profiles of individuals with ASD are varied, and the neurophysiological underpinnings of these developmental difficulties are unclear. While many studies have focused on overall group differences in the amplitude or latency of event related potential (ERP) responses, recent research suggests that increased intra‐subject neural variability may also be a reliable indicator of atypical brain function in ASD. This study aimed to identify behavioral and neural variability responses during an emotional inhibitory control task in children with ASD compared to typically developing (TD) children. Children with ASD showed increased variability in response to both inhibitory and emotional stimuli, evidenced by greater reaction time variability and single‐trial ERP variability of N200 and N170 amplitudes and/or latencies compared to TD children. These results suggest that the physiological basis of ASD may be more accurately explained by increased intra‐subject variability, in addition to characteristic increases or decreases in the amplitude or latency of neural responses. Autism Res 2020, 13:221–229. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

The cognitive functions including memory, attention, executive functions, and perception, of individuals with ASD are varied, and the physiological underpinnings of these profiles are unclear. In this study, children with ASD showed increased intra‐subject neural and behavioral variability in response to an emotional inhibitory control task compared to typically developing children. These results suggest that the physiological basis of ASD may also be explained by increased behavioral and neural variability in people with ASD, rather than simply characteristic increases or decreases in averaged brain responses.
An integrated sustainability evaluation of high‐octane gasoline production from lignocellulosic biomass
Authors: Tan Eric C. D.
Published: October 2019

A holistic sustainability analysis for early‐stage biofuel production processes plays a critical role in the improvement of the overall life‐cycle sustainability. Once a conceptual conversion process is developed, the next step is to evaluate its overall sustainability, preferably based on a process sustainability evaluation methodology using various indicators. The US Environmental Protection Agency (EPA)'s Gauging Reaction Effectiveness for the Environmental Sustainability of Chemistries with a Multi‐objective Process Evaluator (GREENSCOPE) methodology evaluates processes in four areas: environment, energy, economics, and efficiency. The method develops relative sustainability scores for indicators that allow comparisons across various technologies. In this study, we implemented GREENSCOPE methodology for a sustainability performance assessment of NREL's conceptual design for the indirect liquefaction of biomass to high‐octane gasoline blendstock by evaluating a range of metrics beyond the typical minimum fuel selling price and greenhouse gas emissions considerations. We applied this methodology to assess the sustainability performance of this gate‐to‐gate conceptual design. One outcome of the sustainability evaluation is to allow researchers to identify process areas in need of sustainability improvement during biofuel production, and the challenges and opportunities for achieving the best possible sustainability targets. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
Storage of Carotenoids in Crustaceans as an Adaptation to Modulate Immunopathology and Optimize Immunological and Life‐History Strategies
Authors: Babin Aurélie , Moreau Jérôme , Moret Yannick
Published: October 2019

Why do some invertebrates store so much carotenoids in their tissues? Storage of carotenoids may not simply be passive and dependent on their environmental availability, as storage variation exists at various taxonomic scales, including among individuals within species. While the strong antioxidant and sometimes immune‐stimulating properties of carotenoids may be beneficial enough to cause the evolution of features improving their assimilation and storage, they may also have fitness downsides explaining why massive carotenoid storage is not universal. Here, the functional and ecological implications of carotenoid storage for the evolution of invertebrate innate immune defenses are examined, especially in crustaceans, which massively store carotenoids for unclear reasons. Three testable hypotheses about the role of carotenoid storage in immunological (resistance and tolerance) and life‐history strategies (with a focus on aging) are proposed, which may ultimately explain the storage of large amounts of these pigments in a context of host–pathogen interactions.
The role of the brain–gut–microbiota axis in psychology: The importance of considering gut microbiota in the development, perpetuation, and treatment of psychological disorders
Authors: Ganci Michael , Suleyman Emra , Butt Henry , Ball Michelle
Published: October 2019

Introduction

The prevalence of psychological disorders remains stable despite steady increases in pharmacological treatments suggesting the need for auxiliary treatment options. Consideration of the brain–gut–microbiota axis (BGMA) has made inroads into reconceptualizing psychological illness from a more holistic perspective. While our understanding of the precise role of gut microbiota (GM) in psychological illness is in its infancy, it represents an attractive target for novel interventions.

Method

An extensive review of relevant literature was undertaken.

Results

Gut microbiota are proposed to directly and indirectly influence mood, cognition, and behavior which are key components of mental health. This paper outlines how GM may be implicated in psychological disorders from etiology through to treatment and prevention using the Four P model of case formulation.

Conclusion

Moving forward, integration of GM into the conceptualization and treatment of psychological illness will require the discipline of psychology to undergo a significant paradigm shift. While the importance of the GM in psychological well‐being must be respected, it is not proposed to be a panacea, but instead, an additional arm to a multidisciplinary approach to treatment and prevention.
Institutional investors' attention to environmental information, trading strategies, and market impacts: Evidence from China
Authors: Wei Ping , Mao Xiaodan , Chen Xiaohong
Published: October 2019

Using a large proprietary database of intraday high‐frequency trading, we investigate the trading strategies of institutional investors in dealing with the negative environmental event disclosure of listed companies and their impact on markets, aiming to reveal the mechanism of the lack of “green efficiency” in China's capital market from the perspective of institutional investors. The results show that institutional investors react to negative environmental events prior to the announcements, indicating premature information leakage in the market; in addition, their trading behaviors mitigate the immediate effect of negative environmental event announcements on stock price. After the event is disclosed, institutional investors engage in short‐term selling and long‐term buy and hold. This trading strategy undermines the irrational selling of individual investors in the event of disclosure, short‐term decline in stock price, and long‐term reversal of market overreaction. In a China context, institutional investors generally take environmental information into consideration. However, they fail to recognize the long‐term value effect of negative environmental events and instead cater to trading strategies towards market volatility.
Nerve dysfunction leads to muscle morphological abnormalities in chronic inflammatory demyelinating polyneuropathy assessed by MRI
Authors: Gilmore Kevin J. , Fanous Jacob , Doherty Timothy J. , Kimpinski Kurt , Rice Charles L.
Published: October 2019

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n= 10) of CIDP patients compared with a healthy age‐matched control group (n= 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413–420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77–84, 2019. © 2019 Wiley Periodicals, Inc.
Healthy lifestyle discussions between healthcare providers and older cancer survivors: Data from 12 cancer centers in the Southeastern United States
Authors: Halilova Karina I. , Pisu Maria , Azuero Andres , Williams Courtney P. , Kenzik Kelly M. , Williams Grant R. , Rocque Gabrielle B. , Martin Michelle Y. , Kvale Elizabeth A. , Demark‐Wahnefried Wendy
Published: October 2019

Background

Little is known about the prevalence of healthy lifestyle (HLS) discussions between providers and older cancer survivors.

Methods

We utilized cross‐sectional data from older cancer survivors (≥65 years) seen at 12 southeastern cancer centers during 2013‐2015. Data on demographics, time since diagnosis, weight, height, and healthy behaviors were collected. Respondents were asked if providers (oncologists, other physicians, and/or nurses) discussed exercise, healthy diet, weight management, and/or smoking cessation during clinical encounters. Descriptive statistics and bivariate associations between HLS topics and survivor characteristics were calculated.

Results

Among 1460 cancer survivors, mean age was 74 years (SD 6), most were white (81%), and >1 year postdiagnosis (84%). The majority (71%) reported discussing at least one of three HLS topics (exercise 49%, healthy diet 53%, vegetable consumption 28%); 17% received counseling on all three. Weight loss was recommended to 33% of overweight/obese survivors and smoking cessation to 85% of current smokers. Oncologists and nurses discussed HLS less frequently compared to other physicians. Younger survivors (65‐74 years) received recommendations for exercise, weight loss, and tobacco cessation more often than older survivors (≥75 years). Compared to white respondents, minorities reported discussions on all topics more often except for tobacco cessation. Excluding tobacco cessation, survivors with recent cancer diagnoses (<1 year) reported HLS discussions more often than survivors >1 year postdiagnosis.

Conclusion

Despite the American Cancer Society's recommendations, older survivors reported a low prevalence of HLS discussions with their providers, with some variation by demographic groups. Strategies are needed to promote these important discussions in this population.
The feasibility of training general practitioners to do cognitive behavioural therapy in routine practice—A qualitative study
Authors: Davidsen Annette Sofie , Overbeck Gritt , Kousgaard Marius Brostrøm
Published: October 2019

Objective

In a collaborative care model in Denmark, general practitioners (GPs) were trained in cognitive behavioural therapy (CBT) of their patients with common mental disorders through supervision by psychiatric nurses and a psychiatrist. We explored the feasibility of implementing CBT as a treatment into routine general practice through this supervision.

Design

A qualitative interview study as part of a larger implementation study of collaborative care between general practice and psychiatry in Denmark.

Method

Interviews with all three professional groups involved in the intervention were analysed using interpretative phenomenological analysis.

Results

The participants experienced several cultural and organizational challenges with implementing CBT in general practice. The GPs were used to carrying out talking therapy with methods integrated into the treatment culture in general practice, and it was difficult for them to supplant existing therapeutic skills and approaches. The specific CBT approach was not compatible with the work conditions and work culture in general practice regarding patient relations, time frames and workload; and the inter‐professional training relations between GPs and psychiatric nurses were often challenging. There was an overall agreement among the professionals that general practice of talking therapy could not be changed in the image of psychiatry.

Conclusion

The results suggest that wide‐scale implementation of CBT delivered by GPs to patients with common mental disorders is not feasible. Nevertheless, there are many psychotherapeutic elements in routine consultations in general practice, and GPs could possibly gain from improving their ways of questioning, and their use of non‐specific therapeutic, relational and psychodynamic factors.
A Theoretical Study of the Molecular Coupled Structures of Aristolochic Acids and Humic Acid, Potential Environmental Contaminants
Authors: Petrescu Alina M. , Lukinich‐Gruia Alexandra T. , Paunescu Virgil , Ilia Gheorghe
Published: October 2019

An understanding of the fate of organic compounds originating from plants in soil is crucial for determining their persistence and concentrations in the environment. Aristolochic acids are believed to be the causal agents that induce Balkan endemic nephropathy by food contamination through soil adsorption of humic acids, major components of soil. Aristolochic acids are active chemicals in Aristolochia plant species found in endemic villages. In this article, molecular structure interactions between 18 structures of aristolochic acids with an inserted humic acid structure were studied. These structures were optimized in vacuo and by periodic box simulation with water solvate using the computational molecular mechanics MM+ method with HyperChem software. The QSPR models were used for correlation of the relationship between the hydrophobicity values of 18 AA structures coupled with a HA structure by MM+ and QSAR+ properties. Computational hydrophobicity values were considered dependent variables and were related to the structural features obtained by molecular and quantum mechanics calculations by multiple linear regression approaches. The obtained model was validated, and the results indicated differing hydrophobicity between the MM+ and QSAR+ properties.
Transcatheter aortic valve replacement versus surgery for symptomatic severe aortic stenosis: A reconstructed individual patient data meta‐analysis
Authors: Dowling Cameron , Kondapally Seshasai Sreenivasa Rao , Firoozi Sami , Brecker Stephen J.
Published: October 2019

Objectives

We wished to undertake a reconstructed individual patient data meta‐analysis of randomized clinical trials comparing transcatheter aortic valve replacement (TAVR) and surgery for patients with severe symptomatic aortic stenosis.

Background

TAVR and surgery are both well‐established methods for treating patients with symptomatic severe aortic stenosis who are at low, intermediate, and high risk for surgery.

Methods

Data were identified by searches of Medline, Embase, CENTRAL and ClinicalTrials.gov for all randomized clinical trials, which compared TAVR and surgery that had published at least 1 year of follow‐up. Individual patient data were reconstructed from Kaplan–Meier curves.

Results

A total of 7,770 patients from seven randomized clinical trials were included in this meta‐analysis. At 1 year, TAVR was associated with a lower risk of death from any cause (hazard ratio [HR], 0.85, 95% confidence interval [CI], 0.73–0.98; p = .03), disabling stroke (HR, 0.71; 95% CI, 0.54–0.93; p = .01) and the composite end point of death or disabling stroke (HR, 0.79; 95% CI, 0.67–0.92; p = .002). Significant interactions were found for access suitability, with TAVR associated with a lower risk of these end points in patients suitable for transfemoral access. TAVR was associated with a lower risk of periprocedural events, whereas the risk of late events was similar between TAVR and surgery.

Conclusions

At 1 year, TAVR was associated with a lower risk of death, disabling stroke and the composite end point, when compared with surgery. These associations were strongest within the subgroup of patients in whom transfemoral access was feasible.
Balanced amino acid and higher micronutrients in millets complements legumes for improved human dietary nutrition
Authors: Anitha Seetha , Govindaraj Mahalingam , Kane‐Potaka Joanna
Published: October 2019

Background and objectives

More than 2 billion people suffer with malnutrition arising from dietary protein and micronutrients deficiencies. To enhance the dietary nutrient quality, the current study used two largely grown varieties of finger millet, pearl millet, pigeonpea, and chickpea to evaluate the effect of millet–legume blends for their enhanced protein digestibility, amino acid profiles, and essential micronutrients.

Findings

Our study revealed the presence of significant levels of proteins (6.3%–22.3%), essential amino acids, and micronutrients (Fe: 2.6–8.5 mg; Zn: 2–5.5 mg; Ca: 22‐450 mg in 100 g) in these varieties. When specific millets combined with legumes in 3:1 proportion, significantly enhanced nutritional value of food by providing a balanced amino acid with good protein digestibility, and high levels of iron (7.58 mg) and zinc (4.96 mg) with 100 g of pearl millet and calcium (400.57 mg) with 100 g of finger millet.

Conclusions

Pigeonpea and chickpea have a good level of proteins with essential amino acids except methionine and cysteine, whereas millet had balanced amino acid including methionine and cysteine (50% higher) and much higher levels of micronutrients (Fe, Zn and Ca). Therefore, specific millets and legumes combination complemented higher levels of micronutrients in addition to complete proteins to support comprehensive human nutrition.

Significance and novelty

This study opens prospects for selecting complementary nutrient‐dense varieties for household consumption. Industries can explore these product developments significantly to reduce malnutrition if consumed adequately, which is not possible with polished rice, refined wheat flour or maize even if it is combined with legumes.
Reduction of Propanoic Acid over Pd‐Promoted Supported WOx Catalysts
Authors: Kammert James D. , Brezicki Gordon , Miyake Naomi , Stavitski Eli , Davis Robert J.
Published: October 2019

Silica‐, titania‐, and zirconia‐supported tungsten oxide catalysts were synthesized by wetness impregnation techniques. When promoted with Pd, these materials catalyzed the reduction of propanoic acid to 1‐propanol at 433 K with a selectivity of up to 92 % (13.5 % conversion) in atmospheric pressure of H2. Over Pd‐promoted WOx/TiO2, the observed orders of reaction were 0.2 in H2 and 0.7 in propanoic acid, and the apparent activation energy was 54 kJ mol−1. In situ X‐ray absorption spectroscopy of Pd‐promoted WOx/SiO2 revealed a slight reduction of the W from +6 to an average oxidation state of about +5 during H2 treatment above 473 K. In situ infrared spectroscopy indicated the catalyst surface was covered mostly by propanoate species during reaction. For comparison, supported phosphotungstic acid was also evaluated as a catalyst under identical conditions, but the resulting high acidity of the catalyst was deleterious to alcohol selectivity.
Systematic evaluation of PAXgene® tissue fixation for the histopathological and molecular study of lung cancer
Authors: Southwood Mark , Krenz Tomasz , Cant Natasha , Maurya Manisha , Gazdova Jana , Maxwell Perry , McGready Claire , Moseley Ellen , Hughes Susan , Stewart Peter , Salto‐Tellez Manuel , Groelz Daniel , Rassl Doris ,   On behalf of the STRATfix Consortium
Published: October 2019

Whilst adequate for most existing pathological tests, formalin is generally considered a poor DNA preservative and use of alternative fixatives may prove advantageous for molecular testing of tumour material; an increasingly common approach to identify targetable driver mutations in lung cancer patients. We collected paired PAXgene® tissue‐fixed and formalin‐fixed samples of block‐sized tumour and lung parenchyma, Temno‐needle core tumour biopsies and fine needle tumour aspirates (FNAs) from non‐small cell lung cancer resection specimens. Traditionally processed formalin fixed paraffin wax embedded (FFPE) samples were compared to paired PAXgene® tissue fixed paraffin‐embedded (PFPE) samples. We evaluated suitability for common laboratory tests (H&E staining and immunohistochemistry) and performance for downstream molecular investigations relevant to lung cancer, including RT‐PCR and next generation DNA sequencing (NGS). Adequate and comparable H&E staining was seen in all sample types and nuclear staining was preferable in PAXgene® fixed Temno tumour biopsies and tumour FNA samples. Immunohistochemical staining was broadly comparable. PFPE samples enabled greater yields of less‐fragmented DNA than FFPE comparators. PFPE samples were also superior for PCR and NGS performance, both in terms of quality control metrics and for variant calling. Critically we identified a greater number of genetic variants in the epidermal growth factor receptor gene when using PFPE samples and the Ingenuity® Variant Analysis pipeline. In summary, PFPE samples are adequate for histopathological diagnosis and suitable for the majority of existing laboratory tests. PAXgene® fixation is superior for DNA and RNA integrity, particularly in low‐yield samples and facilitates improved NGS performance, including the detection of actionable lung cancer mutations for precision medicine in lung cancer samples.
The association between hyperuricemia and coronary artery calcification development: A systematic review and meta‐analysis
Authors: Liang Ling , Hou Xianghua , Bainey Kevin R. , Zhang Yanlin , Tymchak Wayne , Qi Zhongquan , Li Weihua , Banh Hoan Linh
Published: October 2019

Hyperuricemia coincides with coronary artery calcification (CAC) development, but the role of serum uric acid (SUA) as a risk factor for CAC remains unclear. The objective of this study was to gain an insight into the association between SUA and CAC in adults by performing a meta‐analysis. MEDLINE, EMBASE, the Cochrane Library, and EBSCO (CINAHL) were searched for relevant observational studies published until 2 June 2019. Studies were included only if they reported data on CAC presence (Agatston score > 0) or progression related to hyperuricemia in subclinical adult patients. The pooled estimates of crude and adjusted odds ratios (ORs) and 95% confidence interval (CI) were calculated to evaluate the association between CAC presence or progression and hyperuricemia. A total of 11 studies were identified involving 11 108 adults. The pooled OR based on the frequency of CAC presence showed that patients in the high SUA group had 1.806‐fold risk for developing CAC (95% CI: 1.491‐2.186) under the minimal threshold of hyperuricemia (more than 6 mg/dL or 357 μmoL/L). When SUA levels were analyzed as categorical variables, the pooled estimate of adjusted ORs was 1.48 (95% CI: 1.23‐1.79) for CAC presence. Additionally, for each increase of 1 mg/dL of SUA level, the risk of CAC progression was increased by 31% (95% CI: 1.15‐1.49) with an average follow‐up duration ranged from 4.6 to 6.1 years. Hyperuricemia is closely associated with increased risk of CAC development and CAC progression in asymptomatic patients.
Longitudinal prognostic communication needs of adolescents and young adults with cancer
Authors: Sisk Bryan A. , Fasciano Karen , Block Susan D. , Mack Jennifer W.
Published: October 2019

Background

Although the majority of adolescent and young adult (AYA) patients with cancer desire prognostic information, to the authors' knowledge little is known regarding how preferences for prognostic communication change over time.

Methods

The current study was a longitudinal, prospective, questionnaire‐based cohort study of 136 AYA patients with cancer who were aged 15 to 29 years and who were treated at a large academic cancer center. Previously published scales were administered at the time of diagnosis and at 4 months and 12 months after diagnosis.

Results

The majority of patients reported that prognostic information was very/extremely important at the time of diagnosis (85%), at 4 months (96%; P = .002 compared with baseline), and at 12 months (81%; P = .02 compared with baseline). Few patients reported that prognostic knowledge was very/extremely upsetting at baseline (7%), at 4 months (9%; P = .44 compared with baseline), or at 12 months (11%; P = .27 compared with baseline). The majority of patients were satisfied with the amount of prognostic information received throughout the year after diagnosis (81%, 86%, and 81%, respectively, at the time of diagnosis, at 4 months, and at 12 months). This percentage did not change between the time of diagnosis and 4 months (P = .16) or between diagnosis and 12 months (P = 1.00). In multivariable analysis, satisfaction with prognostic information received was associated with patient report of high‐quality communication (odds ratio, 2.67; 95% CI, 1.38‐5.17) and having a >75% chance of cure (odds ratio, 2.39; 95% CI, 1.24‐4.61) after adjustment for patient age category, race/ethnicity, and time point of administration.

Conclusions

The majority of AYA patients with cancer were satisfied with prognostic disclosure over time, but a sizeable minority wanted additional information. Desire for prognostic information increased over time. Clinicians should return to prognostic discussions over time to support AYA patients with cancer.
The mouse olfactory peduncle 4: Development of synapses, perineuronal nets, and capillaries
Authors: Collins Lindsay N. , Brunjes Peter C.
Published: October 2019

Olfaction is critical for survival in neonatal mammals. However, little is known about the neural substrate for this ability as few studies of synaptic development in several olfactory processing regions have been reported. Odor information detected in the nasal cavity is first processed by the olfactory bulb and then sent via the lateral olfactory tract to a series of olfactory cortical areas. The first of these, the anterior olfactory nucleus pars principalis (AONpP), is a simple, two layered cortex with an outer plexiform and inner cell zone (Layers 1 and 2, respectively). Five sets of studies examined age‐related changes in the AONpP. First, immunocytochemistry for glutamatergic (VGlut1 and VGlut2) and GABAergic (VGAT) synapses demonstrated that overall synaptic patterns remained uniform with age. The second set quantified synaptic development with electron microscopy and found different developmental patterns between Layers 1 and 2. As many of the interhemispheric connections in the olfactory system arise from AONpP, the third set examined the development of crossed projections using anterograde tracers and electron microscopy to explore the maturation of this pathway. A fourth study examined ontogenetic changes in immunostaining for the proteoglycans aggrecan and brevican, markers of mesh‐like extracellular structures known as perineuronal nets whose maturation is associated with the end of early critical periods of synaptogenesis. A final study found no age‐related changes in the density of vasculature in the peduncle from P5 to P30. This work is among the first to examine early postnatal changes in this initial cortical region of the olfactory system.
Are Novel, Nonrandomized Analytic Methods Fit for Decision Making? The Need for Prospective, Controlled, and Transparent Validation
Authors: Eichler Hans‐Georg , Koenig Franz , Arlett Peter , Enzmann Harald , Humphreys Anthony , Pétavy Frank , Schwarzer‐Daum Brigitte , Sepodes Bruno , Vamvakas Spiros , Rasi Guido
Published: October 2019

Real‐world data and patient‐level data from completed randomized controlled trials are becoming available for secondary analysis on an unprecedented scale. A range of novel methodologies and study designs have been proposed for their analysis or combination. However, to make novel analytical methods acceptable for regulators and other decision makers will require their testing and validation in broadly the same way one would evaluate a new drug: prospectively, well‐controlled, and according to a pre‐agreed plan. From a European regulators' perspective, the established methods qualification advice procedure with active participation of patient groups and other decision makers is an efficient and transparent platform for the development and validation of novel study designs.
Does intraoperative bone density testing correlate with parameters of primary implant stability? A pilot study in minipigs
Authors: Grobecker‐Karl Tanja , Palarie Victor , Schneider Sonja , Karl Matthias
Published: October 2019

Objectives

Bone density, surgical protocol, and implant design are the major determinants of primary stability. The goal of this animal trial was to investigate potential correlations of intraoperative bone density testing with clinical and histologic parameters of primary implant stability.

Material and methods

Following extractions of all mandibular premolars and subsequent healing, four implants each were placed in a total of four minipigs. Bone density was determined by applying intraoperative compressive tests using a device named BoneProbe whereas measurements of implant insertion torque and resonance frequency analysis were used for evaluating implant stability. Bone mineral density (BMD) and bone to implant contact were quantified after harvesting mandibular block sections. Spearman rank correlation tests were performed for evaluating correlations (α = .05).

Results

Due to variation in clinical measurements, only weak correlations could be identified. A positive correlation was found between the parameters bone to implant contact and BMD (Spearman's rho .53; p = .05) whereas an inverse correlation was observed between BMD and implant stability (Spearman's rho −.61; p = .03). Both BoneProbe measurements in the cortical and trabecular area positively correlated with implant insertion torque (Spearman's rho 0.60; p = .02). A slightly stronger correlation was observed between the average of both BoneProbe measurements and implant insertion torque (Spearman's rho.66; p = .01).

Conclusions

While establishing exact relationships among parameters of implant stability and the measurement techniques applied would require greater sample size, intraoperative compressive testing of bone might, despite the weak correlations seen here, be a useful tool for predicting primary implant stability.
Does environmental regulation policy help improve green production performance? Evidence from China's industry
Authors: Wang Chao , Zhang Yue‐Jun
Published: October 2019

Environmental regulation (ER) policy is an effective means to improve green production performance (GPP), but how ER policy will affect China's GPP remains to be studied. Therefore, with the panel data of 38 industrial sectors in China during 2004–2015, we employ the continuous difference in difference method and system generalised method of moment method to estimate the impact of ER policy on GPP in the heavily polluting sectors of China. The empirical results show that first, the implementation of ER policy does not significantly improve GPP of heavily polluting sectors during the sample period. Among them, the external technological progress and export learning effect are important factors that hinder their GPP. Second, ER has no lag effect on GPP of 38 industrial sectors, and the increase in research and development investment does not significantly improve GPP. Finally, foreign direct investment has promoted GPP in China's industrial sectors to some extent.
A modified flow cytometry method for objective estimation of human CD4+ regulatory T cells (CD4+ Tregs) in peripheral blood, via CD4/CD25/CD45RO/FoxP3 labeling
Authors: Petsiou Asimina , Paschou Stavroula A. , Vartholomatos Georgios , Chatzigianni Katerina , Kolaitis Nikolaos , Giotaki Eleni , Bondinas George P. , Moustakas Antonis K. , Karamoutsios Achilleas , Zervou Eleftheria , Tigas Stelios , Tsatsoulis Agathocles , Papadopoulos George K.
Published: October 2019

Background

Several methods exist for flow‐cytometric estimation of human peripheral blood CD4+ T regulatory cells (CD4+ Tregs).

Methods

We report our experience with the estimation of human CD4+ Tregs via three different characterizations using flow cytometry (CD25highFoxP3+, CD25highCD127low/−FoxP3+, and CD4+CD25high/intCD45ROFoxP3+) in normal subjects. We have used these methods on the control populations from two studies (32 and 36 subjects, respectively), the latter two methods retrospectively on the subjects of the first study. The six CD4+ T cell fractions obtained by the third method were differentially colored to ascertain the distribution of these cell fractions in the CD25/FoxP3, CD45RO/FoxP3, and CD25/CD127 dot plots from CD4/CD25/CD45RO/FoxP3 and CD4/CD25/CD45RO/CD127 panels.

Results

Each approach gives significantly different estimates of Tregs (expressed as percentage of CD4+ T cells), with the second almost invariably yielding higher percentages than the other two. Only the third approach can distinguish among effector and naïve Tregs and FoxP3+ non‐Tregs. Analysis of CD25/CD127 dot plots reveals that Treg delineation via the widely used definition of CD4+CD25highCD127low/− cells unavoidably yields a mixture of nearly all effector and most of naïve Tregs, as well as FoxP3+ non‐Tregs plus other cells. Delineation of effector/naïve Tregs and FoxP3+ non‐Tregs is possible via CD45RO/CD25 dot plots but not by CD45RO/FoxP3 counterparts (as done previously) because of overlapping FoxP3 intensities among Tregs and non‐Tregs.

Conclusion

Our comparison shows that CD4/CD25/CD45RO/FoxP3 panels are an objective means of estimating effector and naïve Tregs via colored dot plots, aiding thus in Treg delineation in health and detecting aberrations in disease.
Diagnosis of paroxysmal nocturnal hemoglobinuria with flowcytometry panels including CD157: Data from the real world
Authors: Zhang Yuesheng , Ding Jing , Gu Haihui , Guo Mengqiao , Wu Jiawei , Xu Huangmeng , Wang Ziwei , Yang Jianmin , Tang Gusheng
Published: October 2019

Background

Several studies have used CD157 in white blood cells with or without proaerolysin (fluorescein‐labeled proaerolysin [FLAER])‐based flow cytometry assays in the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH).

Methods

We designed a seven‐color CD marker panel comprising FLAER, CD15, CD64, CD24, CD14, CD157, and CD45 to verify CD157's clinical applicability and diagnostic performance in a clinical setting.

Results

A total of 356 samples were tested. These included 43 PNH‐positive samples and 313 PNH‐negative samples. PNH clones confirmed by the CD157/FLAER combination were almost identical in size to the clones detected by the CD24/CD14/FLAER combination, and the accuracy of the CD157/FLAER combination was 100% in granulocytes and 99.7% in monocytes. Substitution of FLAER with CD157 resulted in 1.9% and 3.5% false‐positives in granulocytes and monocytes, respectively. The accuracy was 98.3% and 96.9% in granulocytes and monocytes, respectively. Moreover, the loss of CD157 expression in granulocytes and monocytes was commonly observed in non‐PNH patients. Some monocytes in non‐PNH patients had weak expression of CD14 but normal expression of FLAER. In this study, PNH clones in granulocytes were always lower than those in matched monocytes.

Conclusions

We performed the first prospective exploration of the clinical usefulness of FLAER and CD157 in simultaneously recognizing PNH clones in granulocytes and monocytes and verified the applicability of CD157 in substitute for both CD14 and CD24. In the conditions where FLAER is not available, substitution of FLAER with CD157 is acceptable for the identification of PNH clones under the premise of giving full attention to the potential for false‐positives.
Positional Information—A concept underpinning our understanding of developmental biology
Authors: Vargesson Neil
Published: October 2019

It is now 50 years since Lewis Wolpert published the paper in which he set out the concept of Positional Information to explain how spatial patterns of cellular differentiation are generated. This concept has provided a universal model for pattern formation in embryonic development and regeneration and become part of the fabric of the field of developmental biology. Here I outline how Wolpert devised the concept of Positional Information and describe landmark studies from his lab investigating how Positional Information is specified in the developing chick limb.
The acquisition of positional information across the radial axis of the cochlea
Authors: Munnamalai Vidhya , Fekete Donna M.
Published: October 2019

The mammalian cochlea detects sound and transmits this information to the brain. A cross section through the cochlea reveals functionally distinct epithelial domains arrayed around the circumference of a fluid‐filled duct. Six major domains include two on the roof of the duct (Reissner's membrane medially and the stria vascularis laterally) and four across the floor of the duct, including the medial and lateral halves of the sensory domain, the organ of Corti. These radial domains are distinguishable in the embryonic cochlea by differential expression of transcription factors, and we focus here on a subset of the factors that can influence cochlear fates. We then move upstream of these genes to identify which of five signaling pathways (Notch, Fgf, Wnt, Bmp, and Shh) controls their spatial patterns of expression. We link the signaling pathways to their downstream genes, separating them by their radial position, to create putative gene regulatory networks (GRNs) from two time points, before and during the time when six radial compartments arise. These GRNs offer a framework for understanding the acquisition of positional information across the radial axis of the cochlea, and to guide therapeutic approaches to repair or regenerate distinct cochlear components that may contribute to hearing loss.
Winter recreation and Canada lynx: reducing conflict through niche partitioning
Authors: Squires John R. , Olson Lucretia E. , Roberts Elizabeth K. , Ivan Jacob S. , Hebblewhite Mark
Published: October 2019

Outdoor recreationists are important advocates for wildlife on public lands. However, balancing potential impacts associated with increased human disturbance with the conservation of sensitive species is a central issue facing ecologists and land managers alike, especially for dispersed winter recreation due to its disproportionate impact to wildlife. We studied how dispersed winter recreation (outside developed ski areas) impacted a reintroduced meso‐carnivore, Canada lynx (Lynx canadensis), at the southern periphery of the species’ range in the southern Rocky Mountains. On a voluntary basis, we distributed global positioning system (GPS) units to winter recreationists and documented 2143 spatial movement tracks of recreationists engaged in motorized and nonmotorized winter sports for a total cumulative distance of 56,000 km from 2010 to 2013. We also deployed GPS radio collars on adult Canada lynx that were resident in the mountainous topography that attracted high levels of dispersed winter recreation. We documented that resource‐selection models (RSFs) for Canada lynx were significantly improved when selection patterns of winter recreationists were included in best‐performing models. Canada lynx and winter recreationists partitioned environmental gradients in ways that reduced the potential for recreation‐related disturbance. Although the inclusion of recreation improved the RSF model for Canada lynx, environmental covariates explained most variation in resource use. The environmental gradients that most separated areas selected by Canada lynx from those used by recreationists were forest canopy closure, road density, and slope. Canada lynx also exhibited a functional response of increased avoidance of areas selected by motorized winter recreationists (snowmobiling off‐trail, hybrid snowmobile) compared with either no functional response (hybrid ski) or selection for (backcountry skiing) areas suitable for nonmotorized winter recreation. We conclude with a discussion of implications associated with providing winter recreation balanced with the conservation of Canada lynx.
Alkynyl Fischer Carbenes as a Platform for the Production of Difluorodiazaborinine Complexes via β‐Amino‐azadienes
Authors: Benítez‐Puebla Luis J. , López Julio , Flores‐Álamo Marcos , Cruz David Cruz , Peña‐Cabrera Eduardo , Delgado Francisco , Tamariz Joaquín , Vázquez Miguel A.
Published: October 2019

The results of a study of the reactivities of alkynyl Fischer carbenes in the syntheses of diazaborinine derivatives 7a‐i are reported. The strategy employed included the use of β‐amino‐α,β‐unsaturated carbenes (3a–j) with different amines in order to determine the scope of a previously unknown catalytic reaction in the presence of copper salts and anilines. The reaction was highly stereoselective, yielding (Z)‐isomers of the β‐amino‐1‐azadiene framework as the main products (4a–o). As an extension of this research, the compounds 4a–o proved to be suitable precursors for the syntheses of diazaborinine scaffolds in good yields (7a‐i).
Scalable Polymerization Approach to Tailoring Morphologies of Polyimide‐Derived N‐Doped Carbons for High‐Performance Supercapacitors
Authors: Liu Xufei , Mei Peng , Lei Sheng , Zhang Xiaofang , Liu Qian , Yang Yingkui
Published: October 2019

3D N‐doped carbon nanobelt (NCB) networks are fabricated by one‐pot hydrothermal polycondensation of co‐monomer salts of dianhydride and diamine followed by carbonization of the resulting nanobelt‐like polyimides. As control samples, solvothermally polymerized petal‐like polyimides and conventionally polymerized spindle‐like polyimides are also produced, which further yields N‐doped carbon petals and N‐doped carbon spindles after identical carbonization, respectively. Interestingly, all N‐doped carbons copy the morphologies of their polyimide precursors well. Specially, the 800°C‐treated NCB exhibits a robust 3D architecture composed of intertwined nanobelt networks with high N‐doping levels and electroactivity‐enriched N configurations. Remarkably, the symmetric supercapacitor assembled by such NCB electrodes delivers large specific capacitance (193 F g−1 at 1 A g−1), high rate capability (176 F g−1 at 20 A g−1), and long cycling stability (nearly 100% retention over 10,000 cycles at 20 A g−1). The energy density is as high as 27 Wh Kg−1 at the power density of 500 W Kg−1, and retains 24 Wh Kg−1 at the power density up to 20,000 W Kg−1. This work opens up an affordable and scalable approach to the rational fabrication of heteroatom‐contained carbon materials for high‐performance supercapacitors with well‐balanced power and energy output.
Impact of extreme events on conversion efficiency of wave energy converter
Authors: Chakraborty Tilottama , Majumder Mrinmoy
Published: October 2019

Uncontrolled high emission of greenhouse gases due to the use of fossil fuels has high impact on global warming. Due to this global warming, the earth's temperature is increasing and consequently has changed the patterns of various natural phenomena such as wave height and wind speed. Wave power energy resources are ideal alternative to reduce the effects of global warming and climate change. One of the major obstacles lies in the fact that the occurrence of extreme events can jeopardize the wave power plant suspended in the ocean waves. In order to better understand the impact of extreme events on the wave energy generation, a comprehensive analysis of utilization efficiency of wave energy converters with respect to extreme events was conducted in the present investigation with the help of utilization efficiency function (UEF) as an indicative index function. The effect of the extreme events was simulated by the polynomial neural network (PNN) architectures, and change in UEF in the future scenarios was noted. According to the results, the maximum impact on the utilization efficiency of the WEC was observed in the time slab of 2050‐2060, where 5.1% change in utilization efficiency was observed.
A study on a near‐shore cantilevered sea wave energy harvester with a variable cross section
Authors: Zhang Jinfeng , Xie Xiangdong , Song Gangbing , Du Guofeng , Liu Dezheng
Published: October 2019

A cantilevered piezoelectric coupled energy harvester with variable cross section is proposed to obtain the electric power from the longitudinal motion of the near‐shore sea wave. In order to describe the practical process of the sea wave energy harvesting, a mathematical model of the harvester is established based on Airy linear wave theory and Bessel equations to calculate the output charge, voltage, current, and power. Compared to traditional cantilever harvesters with uniform cross section, this harvesting device has a larger energy harvesting efficiency for its more uniform and bigger surface strain in the action of the sea wave. The computation results show a root mean square (RMS) of electric power of 132.6 W can be reached up with the cantilever height, the wave height, and the wavelength of 2.5, 2, and 12.5 m, respectively, which is 2.41 times of those of the traditional cantilever harvester with uniform cross section. In addition, the output powers of the harvester in tiding and in array are also discussed. This research provided a new practical and efficient method of harvesting near‐shore sea wave energy to supply the electric power demand of the households near seaside.