bluuebunny/crossref_metadata_2025 huggingface dataset:
Restructuring Requirements Analysis Using Model‐Based Systems Engineering and Agile Systems Engineering
Authors: Smith Warren B. , Castro Lymari
Published: July 2018

In 2009, the US Army initiated a large acquisition program to modernize one of its systems. Due to circumstances, the program had to accelerate the system requirements review (SRR) milestone from eighteen months to five months. This paper describes the new agile requirements analysis process used, which accomplished this seventy percent schedule reduction. The process consisted of using model‐based systems engineering (MBSE), storyboarding techniques, collaborative daily analysis of system and subsystems requirements, and the iterative and incremental delivery of requirements which engineers used for the SRR. The paper focuses on the practical application of an agile systems engineering requirements analysis and its benefits to manage caprice, uncertainty, risk, variation, and evolution (CURVE) in a large US Department of Defense (DoD) program while reducing the deployment time.
Overcoming the Challenges of Agile for Globally Distributed Industrial Research
Authors: Smiley Karen J. , Louis Catherine L. , Augustine Vinay , Sharma Saumya , Nistor Iulian , Cordes Andrew , Becker Oliver
Published: July 2018

This paper summarizes the initial experiences and lessons learned while enabling and practicing agile methods at an industrial research lab. Lab staff are highly‐educated personnel who innovate in complex mixed hardware/software systems, software‐intensive systems, hardware components, and systems of systems. We discuss our goals in introducing agile, the challenges we faced with globally distributed industrial research in our capricious, uncertain, risky, variable, and evolving (CURVE) domains, how we addressed these challenges, results and lessons learned to date, and our next steps.
Longtime driving induced cerebral hemodynamic elevation and behavior degradation as assessed by functional near‐infrared spectroscopy and a voluntary attention test
Authors: Li Ting , Lin Yu , Gao Yuan , Zhong Fulin
Published: July 2018

Drowsy driving contributes to ~20% of all traffic accidents worldwide. Onsite monitoring the mental condition of a driver and forewarning may be a preventive solution to reduce occurrence of drowsiness and potential accidents. Functional near‐infrared spectroscopy (fNIRS) has been successfully utilized in hemodynamics‐interpreted functional activity in preliminary voluntary attention experiments. Here, we monitored hemodynamic alternations using fNIRS upon the prefrontal cortex over 13 volunteers in the course of a 7‐hour driving simulation and evaluated their reaction capability with a voluntary attention test based on Go/NoGo paradigm. A degradation in attention test score (Accuracy/RT) as well as the elevations in oxy‐hemoglobin (Δ[HbO2]) and total hemoglobin (Δ[tHb]) were found significantly correlated with driving duration (Accuracy/RT: r = −0.964, P < 0.001; Δ[HbO2]: r = 0.950, P < 0.001; Δ[tHb]: r = 0.852, P = 0.007). The hemodynamic parameters are in significant inverse correlations with Accuracy/RT (Δ[HbO2]: r = −0.896, p = 0.003; Δ[tHb]: r = −0.844, P = 0.008), indicating the potential to forewarn drivers the attention degradation with onsite fNIRS measurements.
A promising, novel index in the diagnosis and follow‐up of patent ductus arteriosus: Red cell distribution width‐to‐platelet ratio
Authors: Özer Bekmez Buse , Tayman Cüneyt , Büyüktiryaki Mehmet , Çetinkaya Aslıhan Köse , Çakır Ufuk , Derme Turan
Published: July 2018

Background

The role of red cell distribution width‐to‐platelet ratio (RPR) has not previously been mentioned in reports on patent ductus arteriosus (PDA). Our objective was to evaluate whether RPR would have a role in the diagnosis and/or prediction of pharmacological closure of PDA.

Methods

Preterm infants’ gestational age ≤30 weeks and ≤1500 g who were given first ibuprofen treatment in the first week of life for hemodynamically significant PDA (hsPDA) were included in the study. The patients were matched for gestational age, birthweight, and sex. Patients were subdivided into two groups based on the response to medical treatment (open and closed PDA). Hemogram parameters were recorded before and after medical therapy. Groups were compared with regard to demographic and clinical characteristics and for three sequential hematological parameters. RPR was calculated. Patients with sepsis, anemia, perinatal asphyxia, and congenital/chromosomal anomaly were not included in the study.

Results

A total of 112 infants had medically treated hsPDA. Of those, ductus closed in 70 neonates (closed PDA). A total of 96 infants constituted the control group. Mean gestational age and birthweight of the patients were 28.9 ± 2.4 weeks and 1207 ± 372 g. While RPR was significantly increased, PCT was lower in both hsPDA and open PDA groups (P < 0.05 and P < 0.05, respectively). In multivariate analysis, high RPR (OR 3.3, 95% CI 1.438‐5.872, P < 0.05) and RDS (OR 2.9, 95% CI 1.903‐4.811, P < 0.01) were detected as independent risk factors for hsPDA.

Conclusion

Red cell distribution width‐to‐platelet ratio and PCT may be promising supportive tools for the diagnosis and prediction of pharmacotherapy success.
Recent research progress on bio‐oil conversion into bio‐fuels and raw chemicals: a review
Authors: Valle Beatriz , Remiro Aingeru , García‐Gómez Naiara , Gayubo Ana G , Bilbao Javier
Published: July 2018

Recent advances in lignocellulosic biomass valorization for producing fuels and commodities (olefins and BTX aromatics) are gathered in this paper, with a focus on the conversion of bio‐oil (produced by fast pyrolysis of biomass). The main valorization routes are: (i) conditioning of bio‐oil (by esterification, aldol condensation, ketonization, in situ cracking, and mild hydrodeoxygenation) for its use as a fuel or stable raw material for further catalytic processing; (ii) production of fuels by deep hydrodeoxygenation; (iii) ex situ catalytic cracking (in line) of the volatiles produced in biomass pyrolysis, aimed at the selective production of olefins and aromatics; (iv) cracking of raw bio‐oil in units designed with specific objectives concerning selectivity; and (v) processing in fluidized bed catalytic cracking (FCC) units. This review deals with the technological evolution of these routes, in terms of catalysts, reaction conditions, reactors, and product yields. A study has been carried out on the current state‐of‐knowledge of the technological capacity, advantages and disadvantages of the different routes, as well as on the prospects for the implementation of each route within the scope of the Sustainable Refinery. © 2018 Society of Chemical Industry
Early experience with a low FODMAP diet in Asian patients with irritable bowel syndrome
Authors: Wong Zhiqin , Mok Chu‐Zhen , Majid Hazreen Abdul , Mahadeva Sanjiv
Published: July 2018

Background

The efficacy and acceptance of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet in Asian adults with irritable bowel syndrome (IBS) remain uncertain. We aimed to describe our early experience in a single center with a dedicated gastroenterology dietetic service.

Methods

Consecutive patients with IBS referred to our dedicated Dietetic Gastroenterology Clinic between February 2016 and May 2016 were screened. A low FODMAP diet was instituted as per standard protocol. Data on demographic and clinical variables were obtained from patients’ records and prospective telephone interviews.

Results

A total of 16 patients, with a median age of 67 ± 13.57 years; female gender n = 10 (62.5%); ethnicity: Chinese n = 8 (50%), Indian n = 5 (31.25%), and Malay n = 3 (18.75%) with IBS, were included in the study. Compliance with the low FODMAP diet was complete in 8 of 16 (50%) patients, partial in 4 of 16 (25%), and 4 of 16 (25%) could not comply with the diet at all. Improvement in symptoms were reported in 11 of 16 (68.8%) patients. Among patients who complied (complete/partial) with the low FODMAP diet, predominant symptom improvement was reported as follows: abdominal pain 3 of 5 (60%), abdominal bloating/distension 7 of 10 (70%), and flatulence 7 of 8 (87.5%). Patients with the IBS‐D subtype appeared to have the greatest improvement in stool consistency (87.5% IBS‐D vs 12.5% non‐IBS‐D, P = 0.009).

Conclusion

Based on our pilot observational study of a relatively small sample of Asian IBS patients, compliance with a low FODMAP diet appears to be low. Further larger studies are required to verify our observation.
Molecular epidemiology of noroviruses in children in South Greece, 2013‐2015
Authors: Siafakas Nikolaos , Zerva Loukia , Hatzaki Despina , Lebessi Evangelia , Chronopoulou Genovefa , Paraskakis Irene , Pournaras Spyridon
Published: July 2018

Noroviruses constitute the leading cause of acute, nonbacterial gastroenteritis that affects both children and adults in healthcare and community settings. The current study attempted to provide insight on the molecular epidemiology of noroviruses in children in South Greece. Genotypic characterization of 69 norovirus strains detected in stool samples from children with gastroenteritis during a period of 30 months (January 2013 to June 2015) was performed on the basis of ORF2 (VP1 capsid) gene sequences. The results revealed the circulation of a diverse variety of norovirus genotypes. GII.4 was the predominant genotype (74%), followed by GII.2 (8.7%), GII.3 (5.8%), GII.6 (2.9%), GI.2 (2.9%), and four strains identified as GII.1, GII.7, GII.8, and GII.13, respectively. Phylogenetic analysis showed that most of the strains were closely associated with norovirus strains that circulated globally either in outbreaks and sporadic cases of gastroenteritis or in the environment during the last 4 years. Οf the GII.4 strains, 80.4% were detected between January 2013 and February 2014, indicating a possible ongoing epidemic. The incidence of other genotypes remained constant throughout the study period. Genotypic and phylogenetic analysis showed the predominance of the “Sydney 2012” variant among the GII.4 strains, whereas one GII.4 strain was identified as a “New Orleans 2009” variant. Five GII.4 strains showed significant nucleotide and amino acid sequence divergence from either the “Sydney 2012” or the “New Orleans 2009” variant, and these divergent strains might represent an emerging GII.4 variant.
Time‐resolved Raman spectroscopy for shock‐driven intramolecular electron redistribution of cyclotrimethylene trinitramine (RDX)
Authors: Yu Guoyang , Zheng Zhaoyang , Wu Honglin , Zeng Yangyang , Wu Qiang , Tan Duowang , Zheng Xianxu , Song Yunfei , Yang Yanqiang
Published: July 2018

Shock‐driven intramolecular electron redistribution (IER) of cyclotrimethylene trinitramine (RDX) is proposed, which will be helpful for understanding the initiation and safety mechanisms of RDX materials under shock compressions. Laser‐driven shock wave was performed to generate a dynamic pressure, and time‐resolved Raman spectroscopy was used to probe the shock wave response of RDX. First‐principle calculations were utilized to identify Raman modes and determine a pressure‐dependent electron density distribution in RDX molecules. Raman peaks of RDX have blue shifts under shock loadings, which are caused by IER. According to calculations, it can be confirmed that electrons transfer from C–H and N–O bonds to N–N bonds under shock loadings in IER. We suggest that shock‐driven IER will make some chemical bonds be broken more easily under shock conditions.
131‐Oxophorbine protopheophorbide A from Ziziphus lotus as a novel mesenchymal‐epithelial transition factor receptor inhibitory lead for the control of breast tumor growth in vitro and in vivo
Authors: Souid Soumaya , Elsayed Heba E. , Ebrahim Hassan Y. , Mohyeldin Mohamed M. , Siddique Abu Bakar , Karoui Habib , El Sayed Khalid A. , Essafi‐Benkhadir Khadija
Published: July 2018

The failure of chemotherapy especially in triple negative breast cancer (TNBC) patients has been correlated with the overexpression of the mesenchymal‐epithelial transition factor (c‐Met) receptor. Thus, the hepatocyte growth factor (HGF)/c‐Met signaling axis has gained considerable attention as a valid molecular target for breast cancer therapy. This study reports for the first time the discovery of the 131‐oxophorbines pheophorbide A and protopheophorbide A along with chlorophyllide A from Ziziphus lotus, an edible typical Tunisian plant, as the potent antiproliferative compounds against the human breast cancer cells MDA‐MB‐231 and MCF‐7. Compared to other compounds, protopheophorbide A exerted the highest light‐independent antiproliferative effect against the metastatic TNBC MDA‐MB‐231 cells (IC50 = 6.5 μM). In silico, this compound targeted the kinase domain of multiple c‐Met crystal structures. It potently inhibited the kinase domain phosphorylation of wild and mutant c‐Met in Z‐LYTE kinase assay. Protopheophorbide A inhibited HGF‐induced downstream c‐Met‐dependent cell proliferation, survival, adhesion and migration through RAF/MEK/ERK and PI3K/PTEN/AKT signaling pathways modulation, ROS generation and activation of JNK and p38 pathways. Interestingly, this compound impaired the ability of the MDA‐MB‐231 cells to adhere at different extracellular matrix proteins by reducing the HGF‐induced expression of integrins αv, β3, α2, and β1. Moreover, protopheophorbide A exhibited anti‐migratory properties (IC50 = 2.2 μM) through impacting the expression levels of E‐cadherin, vimentin, β‐catenin, FAK, Brk, Rac, and Src proteins. Importantly, treatment with protopheophorbide A significantly inhibited the MDA‐MB‐231 tumor growth in vivo. Our results suggest that protopheophorbide A could be a novel c‐Met inhibitory lead with promise to control c‐Met/HGF‐dependent breast malignancies.
Regular Tank Cleaning Is Key to Water Quality
Authors: Schmitt Erin
Published: July 2018

Water storage tanks are generally the most visible and valuable assets in a water distribution system. Regularly cleaning and disinfecting potable water tanks is imperative to providing safe drinking water that meets federal and state regulations.
Preparation of highly cross‐linked hydrophilic porous microspheres poly(N,N′‐methylenebisacrylamide) and poly(N,N′‐methylenebisacrylamide‐co‐acrylic acid) with an application on the removal of cadmium
Authors: Liu Wei , Zhu Xiaolian , Yang Xinlin , Li Ke , Yang Zupeng
Published: July 2018

An effective polymerization system was developed for the synthesis of highly cross‐linked hydrophilic monodispersed microspheres with both the micropores and mesopores inside. A series of poly(N,N′‐methylenebisacrylamide) (PMBA) microspheres with the diameters ranging from 100 to 300 nm were synthesized by distillation precipitation polymerization with N,N‐dimethylacetamide (DMAC) as the porogen, acetonitrile as the solvent, and MBA as the cross‐linker and monomer. The particle size, morphology, and porosity varied according to the variation of the DMAC content. The porosity was determined by physical adsorption of nitrogen, and reached the maximum at 7.5 vol% of DMAC with the specific surface area at 135.8 m2 g−1 and the total pore volume at 0.43 cm3 g−1. The porous and hydrophilic microspheres showed excellent swelling property in water and adsorption property for the Cd(II) in aqueous solution. Meanwhile, carboxylic groups were incorporated into the porous microspheres to achieve porous poly(N,N′‐methylenebisacrylamide‐co‐acrylic acid) (P (MBA‐co‐AA)‐P), which exhibited obvious synergies of the pores and functional groups on the adsorption and provided a perspective application of the Cd(II) removal.
Relationship between clinical severity of “new” bronchopulmonary dysplasia and HRCT abnormalities in VLBW infants
Authors: Sung Tae‐Jung , Hwang Sook M. , Kim Min Y. , Park Shin G. , Choi Ka Y.
Published: July 2018

Background

To assess the relationship between HRCT abnormalities and the clinical severity of “new” bronchopulmonary dysplasia (BPD) and respiratory assistance in <1500 g preterm infants.

Methods

HRCT was performed at the time of discharge in 109 preterm infants with BPD who were born between 2008 and 2014. BPD severity was defined as mild, moderate, or severe according to the NIH diagnostic criteria. Total HRCT scores for each infant were obtained from the sum of the number of BPD lobes assessed by two radiologists: a hyperaeration score (Hs) composed of decreased attenuation, mosaic attenuation, and bulla/bleb, and a parenchyma score (Ps) composed of linear lesions, consolidation, bronchial wall thickening, and bronchiectasis. We compared HRCT scores based on BPD severity and respiratory modes, such as invasive mechanical ventilation (IMV), non‐invasive MV (NIMV), and oxygen therapy.

Results

Among the group of included infants (n = 101), mild BPD was found in 46.5%, moderate BPD in 45.5%, and severe BPD in 7.9%. When partial correlation was adjusted by gestational age (GA) and birth weight, the duration of NIMV was correlated with Ps (r = 0.382, P < 0.001), Hs (r = 0.223, P = 0.027), and total score (r = 0.384, P < 0.001). The duration of oxygen therapy was correlated with Ps (r = 0.374, P < 0.001) and Hs (r = 0.227, P = 0.023). Ps showed a correlation with BPD severity (r = 0.381, P = 0.007) in infants born at ≤26 weeks (GA) and those born at >27 weeks GA (r = 0.298, P = 0.042).

Conclusions

Parenchymal changes showed a greater correlation with the clinical severity of “new” BPD cases, especially in infants born at ≤26 weeks GA. The use of NIMV showed a greater correlation with Ps than Hs.
Overcoming psychosocial challenges in cystic fibrosis: Promoting resilience
Authors: Muther Emily F. , Polineni Deepika , Sawicki Greg S.
Published: July 2018

Individuals living with cystic fibrosis (CF), and their families, have experienced significant improvements in treatment and related research that have enhanced outcomes and survival. Despite such advancement, the burden of living with CF still exists. Many psychosocial stressors and risk factors are associated with the impact of CF. The identification and treatment of such risk factors are discussed throughout this review, with an emphasis on strategies to address psychosocial risk and the importance of promoting resiliency in those touched by CF.
Ga‐68‐PSMA PET/CT in treatment‐naïve patients with prostate cancer: Which clinical parameters and risk stratification systems best predict PSMA‐positive metastases?
Authors: Rogasch Julian M. , Cash Hannes , Zschaeck Sebastian , Elezkurtaj Sefer , Brenner Winfried , Hamm Bernd , Makowski Marcus , Amthauer Holger , Furth Christian , Baur Alexander D. J.
Published: July 2018

Purpose

To evaluate the accuracy of clinical parameters and established pre‐treatment risk stratification systems for prostate cancer (PCa) in predicting PSMA‐positive metastases in men undergoing Ga‐68‐PSMA PET/CT as initial staging examination.

Materials and Methods

A retrospective analysis in 108 consecutive treatment‐naïve patients with biopsy‐proven PCa undergoing Ga‐68‐PSMA PET/CT (median age, 72 years [range, 49‐82 years]) was performed. Prediction of PSMA‐positive metastases by serum PSA, clinical T stage (cT), ISUP group, percentage of positive biopsy cores, and derived risk scores (D'Amico risk classification system, Roach [RF], Yale formula [YF], and Briganti nomogram [BN]) was examined with ROC analysis.

Results

Any PSMA‐positive metastases were found in 36 of 108 patients, including LN metastases in 28 patients, extrapelvic LN metastases in 15 patients, and organ metastases in 19 patients (bone, 19; lung, 1). AUCs for PSA, cT, ISUP, and percentage of positive biopsy cores regarding PSMA‐positive metastases did not differ significantly (range, 0.6‐0.8; each P > 0.05). D'Amico (AUC, 0.61‐0.64) was inferior to RF (0.76‐0.83), YF (0.81‐0.86), and BN (0.73 to 0.88; each P < 0.05). Among the 89 high‐risk patients (D'Amico), decision for or against PET imaging based on RF (cut‐off, >18.0), YF (>10.8), or BN (>8.0) would have prevented PSMA PET/CT in 4 (5%), 15 (17%), or 18 patients (20%), respectively, while preserving a sensitivity ≥95% for PSMA‐positive metastases.

Conclusions

Clinical parameters and established risk stratification systems for PCa can predict Ga‐68‐PSMA PET‐positive metastases in treatment‐naïve patients. Especially YF and BN may improve identification of patients with the highest probability of metastatic disease detected by Ga‐68‐PSMA PET/CT.
Synthesis, Characterization, Analytical and Cytotoxic Studies of N,N′‐Bis(2‐Hydroxynaphthylidene)‐4‐chlorophenyl Methanediamine and Its Co(II), Ni(II) and Cu(II) Complexes
Authors: Amala Subbiah , Santhi Sambamoorthy , Subashini Sungapillai
Published: July 2018

The present study involves one pot synthesis of a novel Schiff base derived from 2‐hydroxy‐1‐naphthaldehyde. Further the Schiff base is used for metal complex preparation. All synthesized compounds are characterized by various spectral and analytical studies. Stoichiometry of the complexes is confirmed by Job's plot method. Of the three complexes, Co(II) complex is found to be the most stable one through UV/Vis titrations and Benesi‐Hildebrand equation. Redox property of the complexes ascertained from CV(Cyclic Voltammetry) confirms catalytic application of the complexes; while fluorescence property of the complexes and the Schiff base indicates chemosensor application of the Schiff base. Both the Schiff base and the complexes are screened against bacterial and fungal pathogens. MIC (Minimum Inhibitory Concentration) studies of the Schiff base and the cobalt complex over Staphylococcus aureus disclose the MIC value as 25 ppm. Cu(II) complex is found to have cytotoxicity against breast cancer cell lines (MCF‐7).
A Systemic Approach to Complex Project Management: Integration of Command‐and‐Control and Network Governance
Authors: Gorod Alex , Hallo Leonie , Nguyen Tiep
Published: July 2018

Projects are becoming more complex given emerging uncertainties that are arising as a result of the exponential growth in technology and the ever‐growing involvement of the human factor. Subsequently, new management approaches are needed to improve project effectiveness and efficiency. This research focuses on identifying the strengths and limitations of two major existing approaches that are fundamentally different in addressing critical issues in complex project management and proposes a new integrative framework. One existing approach, command‐and‐control management, has been proven to be very useful in managing certain types of projects; yet, it can be too rigid to adapt to changes in the environment. On the other hand, network governance, a relatively new existing approach, is flexible and adaptive but lacks conformance and can easily revert to chaos. This paper offers a novel integrative systemic approach, which makes it possible to continuously assess a complex situation and to develop more holistic solutions to project management issues. A case study presented in the paper examines the theoretical application of the new approach in the context of the emergency response and recovery efforts of the Fukushima Daiichi Nuclear Power Plant disaster in Japan. Based on the research related to this incident and the ensuing recovery efforts, it is concluded that existing approaches have not been optimally effective. The proposed approach can bring significant advantages for complex project management by providing flexibility while retaining the ability to regulate the degree of control over the system, as demonstrated through the analysis of the response and recovery of the Fukushima Daiichi case. © 2018 John Wiley & Sons, Ltd.
Escort Clients' Sexual Scripts and Constructions of Intimacy in Commodified Sexual Relationships
Authors: Jones Zoey , Hannem Stacey
Published: July 2018

This article draws on fourteen in‐depth semi‐structured interviews with men who hire female escorts to examine the role of intimacy in their interactions with sex workers. Using the concept of social scripting, we examine the cultural, interpersonal, and intrapsychic meanings that shape the commodified sexual interaction. Focusing on the clients' intrapsychic scripts, we argue that previous typologies of client behavior ignore the role of intimacy and the meaning that individuals ascribe to their own experiences and actions. We suggest a typology of clients that goes beyond previous classifications of “regular” and “non‐regular”—the latter referred to as a “hummingbird” client from the perspective of one sex worker. Our four‐part typology of committed regulars, hybrids, searchers, and industry insiders takes into account the role of intimacy along with the client's perception of frequency and motive, even in seemingly casual sexual encounters. A video abstract is available at https://youtu.be/IK_UiGzWT_E.
Complexity and stability of ecological networks: a review of the theory
Authors: Landi Pietro , Minoarivelo Henintsoa O. , Brännström Åke , Hui Cang , Dieckmann Ulf
Published: July 2018

Our planet is changing at paces never observed before. Species extinction is happening at faster rates than ever, greatly exceeding the five mass extinctions in the fossil record. Nevertheless, our lives are strongly based on services provided by ecosystems, thus the responses to global change of our natural heritage are of immediate concern. Understanding the relationship between complexity and stability of ecosystems is of key importance for the maintenance of the balance of human growth and the conservation of all the natural services that ecosystems provide. Mathematical network models can be used to simplify the vast complexity of the real world, to formally describe and investigate ecological phenomena, and to understand ecosystems propensity of returning to its functioning regime after a stress or a perturbation. The use of ecological‐network models to study the relationship between complexity and stability of natural ecosystems is the focus of this review. The concept of ecological networks and their characteristics are first introduced, followed by central and occasionally contrasting definitions of complexity and stability. The literature on the relationship between complexity and stability in different types of models and in real ecosystems is then reviewed, highlighting the theoretical debate and the lack of consensual agreement. The summary of the importance of this line of research for the successful management and conservation of biodiversity and ecosystem services concludes the review.
Induced pluripotent stem cells (iPSCs) as model to study inherited defects of neurotransmission in inborn errors of metabolism
Authors: Jung‐Klawitter Sabine , Opladen Thomas
Published: July 2018

The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs) has revolutionized the way of modeling human disease. Especially for the modeling of rare human monogenetic diseases with limited numbers of patients available worldwide and limited access to the mostly affected tissues, iPSCs have become an invaluable tool. To study rare diseases affecting neurotransmitter biosynthesis and neurotransmission, stem cell models carrying patient‐specific mutations have become highly important as most of the cell types present in the human brain and the central nervous system (CNS), including motoneurons, neurons, oligodendrocytes, astrocytes, and microglia, can be differentiated from iPSCs following distinct developmental programs. Differentiation can be performed using classical 2D differentiation protocols, thereby generating specific subtypes of neurons or glial cells in a dish. On the other side, 3D differentiation into “organoids” opened new ways to study misregulated developmental processes associated with rare neurological and neurometabolic diseases. For the analysis of defects in neurotransmission associated with rare neurometabolic diseases, different types of brain organoids have been made available during the last years including forebrain, midbrain and cerebral organoids. In this review, we illustrate reprogramming of somatic cells to iPSCs, differentiation in 2D and 3D, as well as already available disease‐specific iPSC models, and discuss current and future applications of these techniques.
Early affective changes and increased connectivity in preclinical Alzheimer's disease
Authors: Fredericks Carolyn A. , Sturm Virginia E. , Brown Jesse A. , Hua Alice Y. , Bilgel Murat , Wong Dean F. , Resnick Susan M. , Seeley William W.
Published: July 2018

Introduction

Affective changes precede cognitive decline in mild Alzheimer's disease and may relate to increased connectivity in a “salience network” attuned to emotionally significant stimuli. The trajectory of affective changes in preclinical Alzheimer's disease, and its relationship to this network, is unknown.

Methods

One hundred one cognitively normal older adults received longitudinal assessments of affective symptoms, then amyloid‐PET. We hypothesized amyloid‐positive individuals would show enhanced emotional reactivity associated with salience network connectivity. We tested whether increased global connectivity in key regions significantly related to affective changes.

Results

In participants later found to be amyloid positive, emotional reactivity increased with age, and interpersonal warmth declined in women. These individuals showed higher global connectivity within the right insula and superior temporal sulcus; higher superior temporal sulcus connectivity predicted increasing emotional reactivity and decreasing interpersonal warmth.

Conclusions

Affective changes should be considered an early preclinical feature of Alzheimer's disease. These changes may relate to higher functional connectivity in regions critical for social‐emotional processing.
Quality of life of persons with permanent colostomy: a phenomenological study
Authors: Alwi Fahrizal ,   Setiawan,   Asrizal
Published: July 2018

Objectives To describe the experiences of persons with permanent colostomy regarding their quality of life.

Methods The study design used descriptive phenomenology following the approach of Collaizzi. There were 12 participants who qualified using purposive sampling based on the inclusion criteria.The data generated were in-depth interviews. Analysis and interpretation used verbatim descriptions.

Results The research data revealed seven themes, namely: limitation in daily living activities, limitations in marital relations and social relationship with others, negative feelings about having the colostomy, financial difficulties, increasing demands of living with colostomy, changes in the needs of rest, physical and expectation of complications, and hoping to live a normal life after colostomy.

Conclusion This study revealed that persons with permanent colostomy experience difficulties and limitations pertaining to daily living activities, including marital and social relations. Importantly, they experience psychological concerns, e.g. having negative feelings about ways of living their lives, including financial difficulties and adjusting to new ways of living. However, there is always the hope to live a normal life. This study provides an understanding of the quality of life of persons with permanent colostomy, allowing nurses to provide appropriate nursing care.
Large-scale structures in a turbulent channel flow with a minimal streamwise flow unit
Authors: Abe Hiroyuki , Antonia Robert Anthony , Toh Sadayoshi
Published: July 2018

Direct numerical simulations are used to examine large-scale motions with a streamwise length$2\sim 4h$($h$denotes the channel half-width) in the logarithmic and outer regions of a turbulent channel flow. We test a minimal ‘streamwise’ flow unit (Toh & Itano,J. Fluid Mech., vol. 524, 2005, pp. 249–262) (or MSU) for larger Kármán numbers ($h^{+}=395$and 1020) than in the original work. This flow unit consists of a sufficiently long (${L_{x}}^{+}\approx 400$) streamwise domain to maintain near-wall turbulence (Jiménez & Moin,J. Fluid Mech., vol. 225, 1991, pp. 213–240) and a spanwise domain which is large enough to represent the spanwise behaviour of inner and outer structures correctly; as$h^{+}$increases, the streamwise extent of the MSU domain decreases with respect to$h$. Particular attention is given to whether the spanwise organization of the large-scale structures may be represented properly in this simplified system at sufficiently large$h^{+}$and how these structures are associated with the mean streamwise velocity$\overline{U}$. It is shown that, in the MSU, the large-scale structures become approximately two-dimensional at$h^{+}=1020$. In this case, the streamwise velocity fluctuation$u$is energized, whereas the spanwise velocity fluctuation$w$is weakened significantly. Indeed, there is a reduced energy redistribution arising from the impaired global nature of the pressure, which is linked to the reduced linear–nonlinear interaction in the Poisson equation (i.e. the rapid pressure). The logarithmic dependence of$\overline{ww}$is also more evident due to the reduced large-scale spanwise meandering. On the other hand, the spanwise organization of the large-scale$u$structures is essentially identical for the MSU and large streamwise domain (LSD). One discernible difference, relative to the LSD, is that the large-scale structures in the MSU are more energized in the outer region due to a reduced turbulent diffusion. In this region, there is a tight coupling between neighbouring structures, which yields antisymmetric pairs (with respect to centreline) of large-scale structures with a spanwise spacing of approximately$3h$; this is intrinsically identical with the outer energetic mode in the optimal transient growth of perturbations (del Álamo & Jiménez,J. Fluid Mech., vol. 561, 2006, pp. 329–358).
Energy flux enhancement, intermittency and turbulence via Fourier triad phase dynamics in the 1-D Burgers equation
Authors: Murray Brendan P. , Bustamante Miguel D.
Published: July 2018

We present a theoretical and numerical study of Fourier-space triad phase dynamics in the one-dimensional stochastically forced Burgers equation at Reynolds number $Re\approx 2.7\times 10^{4}$. We demonstrate that Fourier triad phases over the inertial range display a collective behaviour characterised by intermittent periods of synchronisation and alignment, reminiscent of the Kuramoto model (Chemical Oscillations, Waves, and Turbulence, Springer, 1984) and directly related to collisions of shocks in physical space. These periods of synchronisation favour efficient energy fluxes across the inertial range towards small scales, resulting in strong bursts of dissipation and enhanced coherence of the Fourier energy spectrum. The fast time scale of the onset of synchronisation relegates energy dynamics to a passive role: this is further examined using a reduced system with the Fourier amplitudes fixed in time – a phase-only model. We show that intermittent triad phase dynamics persists without amplitude evolution and we broadly recover many of the characteristics of the full Burgers system. In addition, for both full Burgers and phase-only systems the physical-space velocity statistics reveals that triad phase alignment is directly related to the non-Gaussian statistics typically associated with structure-function intermittency in turbulent systems.
Formation of surface trailing counter-rotating vortex pairs downstream of a sonic jet in a supersonic cross-flow
Authors: Sun Mingbo , Hu Zhiwei
Published: July 2018

Direct numerical simulations were conducted to uncover physical aspects of a transverse sonic jet injected into a supersonic cross-flow at a Mach number of 2.7. Simulations were carried out for two different jet-to-cross-flow momentum flux ratios ($J$) of 2.3 and 5.5. It is identified that collision shock waves behind the jet induce a herringbone separation bubble in the near-wall jet wake and a reattachment valley is formed and embayed by the herringbone recirculation zone. The recirculating flow in the jet leeward separation bubble forms a primary trailing counter-rotating vortex pair (TCVP) close to the wall surface. Analysis on streamlines passing the separation region shows that the wing of the herringbone separation bubble serves as a micro-ramp vortex generator and streamlines acquire angular momentum downstream to form a secondary surface TCVP in the reattachment valley. Herringbone separation wings disappear in the far field due to the cross-interaction of lateral supersonic flow and the expansion flow in the reattachment valley, which also leads to the vanishing of the secondary TCVP. A three-dimensional schematic of surface trailing wakes is presented and explains the formation mechanisms of the surface TCVPs.
Cavity ripple dynamics after pinch-off
Authors: Louf Jean-François , Chang Brian , Eshraghi Javad , Mituniewicz Austin , Vlachos Pavlos P. , Jung Sunghwan
Published: July 2018

During water entry, a projectile can entrain an air cavity that trails behind it. Most previous studies focus on the formation and pinch-off dynamics of the air cavity, but only a few have investigated the long-term cavity dynamics after pinch-off. In this study, we examine the ripple formation following the pinch-off of an air cavity generated by a cone, with different cone angles and impact velocities. The amplitude and wavelength of these ripples are measured, and the force on the cone is experimentally determined. It was observed that the ripple amplitude and wavelength increase linearly with the cone impact velocity, which is predicted by our acoustic model of the compressible air cavity. In addition, the measured force exhibits distinct amplitudes and wavelengths. By measuring the length of the cavity, the resulting pressure variation was averaged inside the air cavity leading to a theoretical force amplitude, which matched our observations. We noted that the force wavelength also follows the same acoustic model, which agrees very well with the wavelength of the ripples.
‘Material contribution’ after Williams v The Bermuda Hospitals Board
Authors: Bailey SH
Published: July 2018

This paper reviews the status of the principle that a claimant can demonstrate a causal link between the defendant's wrongful act or omission and his or her damage by establishing that the act/omission made a ‘material contribution’ to the damage. This principle has been reviewed, in the context of cumulative causes that cannot be ‘compartmentalised’, by the Privy Council in Williams v The Bermuda Hospitals Board. There, the Privy Council regarded the cases of Bonnington Castings v Wardlaw (leaving aside the point as to the divisibility of the disease pneumoconiosis), Bailey v Ministry of Defence and Williams itself as essentially similar to each other. They were to be regarded as cases where the court was entitled to conclude that it was the totality of the exposures/delay in question that caused the ultimate harm. As regards Bailey, this was said in terms not to involve any modification of the but-for test; presumably the same holds good for Bonnington Castings and Williams itself. So orthodoxy appears to be preserved/restored. But is that so?
THE PRESUMPTIONS IN FAVOUR OF MARRIAGE
Authors: Probert Rebecca
Published: July 2018

Eighteenth-century courts needed to rely on presumptions in favour of marriage for a number of reasons, some practical and some legal, but the misleading reporting of one leading nineteenth-century case, followed by institutional changes and a stronger focus on precedent, led to the original evidential assumptions being obscured. A further blurring of the different strands of the presumption occurred in the twenty-first century, leading to confusion in recent cases. Understanding how the much-misunderstood presumptions have developed reveals why they were needed, when they became decoupled from their evidential underpinnings, and how, when and why they should operate today.
Using a distributed lag non-linear model to identify impact of temperature variables on haemorrhagic fever with renal syndrome in Shandong Province
Authors: Xu Qinqin , Li Runzi , Rutherford Shannon , Luo Cheng , Liu Yafei , Wang Zhiqiang , Li Xiujun
Published: July 2018

Haemorrhagic fever with renal syndrome (HFRS) is transmitted to humans mainly by rodents and this transmission could be easily influenced by meteorological factors. Given the long-term changes in climate associated with global climate change, it is important to better identify the effects of meteorological factors of HFRS in epidemic areas. Shandong province is one of the most seriously suffered provinces of HFRS in China. Daily HFRS data and meteorological data from 2007 to 2012 in Shandong province were applied. Quasi-Poisson regression with the distributed lag non-linear model was used to estimate the influences of mean temperature and Diurnal temperature range (DTR) on HFRS by sex, adjusting for the effects of relative humidity, precipitation, day-of-the-week, long-term trends and seasonality. A total of 6707 HFRS cases were reported in our study. The two peaks of HFRS were from March to June and from October to December, particularly, the latter peak in 2012. The estimated effects of mean temperature and DTR on HFRS were non-linear. The immediate and strong effect of low temperature and high DTR on HFRS was found. The lowest temperature −8.86°C at lag 0 days indicated the largest related relative risk (RRs) with the reference (14.85 °C), respectively, 1.46 (95% CI 1.11–1.90) for total cases, 1.33 (95% CI 1.00–1.78) for the males and 1.76 (95% CI 1.12–2.79) for the females. Highest DTR was associated with a higher risk on HFRS, the largest RRs (95% CI) were obtained when DTR = 15.97 °C with a reference at 8.62 °C, with 1.26 (0.96–1.64) for total cases and 1.52 (0.97–2.38) for the female at lag 0 days, 1.22 (1.05–1.41) for the male at lag 5 days. Non-linear lag effects of mean temperature and DTR on HFRS were identified and there were slight differences for different sexes.
Seasonal variation of Pseudomonas aeruginosa in culture positive otitis externa in South East England
Authors: Villedieu A. , Papesh E. , Weinberg S. E. , Teare L. , Radhakrishnan J. , Elamin W. F.
Published: July 2018

Otitis externa is the inflammation of the external auditory canal. The disease is common and shows a seasonal variation with a greater incidence in warmer months. Pseudomonas aeruginosa is a common pathogen in otitis externa and in this retrospective study, we show a corresponding seasonal variation in the proportional incidence of P. aeruginosa isolates from otitis externa in South East England. In total 7770 patients were diagnosed with otitis externa over a period of 9 years from January 2008 to December 2016. P. aeruginosa was isolated from 2802 patients (proportional incidence of 36%). Incidence was higher in the months of August, September and October and in patients between 5 and 15 years of age. We postulate a combination of increased contact with water during warm weather in the holiday season and increased rainfall in the preceding season as a putative mechanism for the seasonal trends.
Analysis of Quiet Time Vertical Ionospheric Delay Gradients Around Suvarnabhumi Airport, Thailand
Authors: Budtho J. , Supnithi P. , Saito S.
Published: July 2018

Global Navigation Satellite System (GNSS) is vital to aircraft navigation at many phases of flight. To extend its use to the approach and landing phases, ground‐based augmentation system is an important on‐the‐ground technology to reduce the positioning errors. However, nonuniform spatial ionospheric delays need to be assessed during ground‐based augmentation system planning at each airport, particularly, in equatorial and low‐latitude regions. In this work, we analyze the statistics of ionospheric delay gradients around Suvarnabhumi airport, Thailand. The ionospheric delay gradients are estimated using single‐frequency code and carrier phase observation through the Kalman filter. To increase the success of the ratio test, the satellite elimination technique is then proposed. Based on the analysis between 2013 and 2016, we find that the background ionospheric delay gradients during equinox are higher than solstice, especially during September equinox 2013 when the gradients are about 9 mm/km. Moreover, the ionospheric delay gradients are more variable during daytime than nighttime.
Avoiding hot-spots in Microwave-assisted Pd/C catalysed reactions by using the biomass derived solvent γ-Valerolactone
Authors: Petricci Elena , Risi Caterina , Ferlin Francesco , Lanari Daniela , Vaccaro Luigi
Published: July 2018

Herein, we report the use of γ-valerolactone as a new biomass-derived reaction medium for microwave assisted organic synthesis. The interaction of this solvent with microwaves and its heating profile under microwave irradiation has been fully characterized for the first time, demonstrating its stability and the applicability in microwave assisted Pd/C catalysed reactions avoiding the arcing phenomena frequently observed in these conditions. The use of γ-valerolactone demonstrated to be compatible with aliphatic and aromatic amines in the hydrogen transfer Pd/C mediated synthesis of benzimidazoles.
RGN-259 (thymosin β4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model
Authors: Kim Chae Eun , Kleinman Hynda K. , Sosne Gabriel , Ousler George W , Kim Kyeongsoon , Kang Sinwook , Yang Jaewook
Published: July 2018

This study evaluated the clinical activity of RGN-259 (thymosin β4) in comparison with cyclosporine A (CsA), diquafosol (DQS), and lifitegrast (LFA) in a murine model of dry eye. The model was NOD.B10-H2b mice in a 30–40% humidified environment together with daily scopolamine hydrobromide injections for 10 days. After desiccation stress, all drugs were evaluated after 10 treatment days. RGN-259 increased tear production similar to that in the DQS- and LFA-treated mice while CsA was inactive. RGN-259 improved corneal smoothness and decreased fluorescein staining similar to that of LFA group while CsA and DQS were inactive. Corneal epithelial detachment was reduced by RGN-259, and DQS and LFA showed similar activity but the CsA was inactive. RGN-259 increased conjunctival goblet cells and mucin production comparable to that seen with CsA, while DQS and LFA were inactive. RGN-259 reduced the over-expression of inflammatory factors comparable to that with CsA and LFA, while DQS was inactive. RGN-259 increased mucin production comparable to that observed with CsA, while DQS and LFA were inactive. In conclusion, RGN-259 promoted recovery of mucins and goblet cells, improved corneal integrity, and reduced inflammation in a dry eye mouse model and was equal to or more effective than prescription treatments.
Autoantigen-Harboring Apoptotic Cells Hijack the Coinhibitory Pathway of T Cell Activation
Authors: Yakoub Abraam M. , Schulz Ralph , Seiffert Martina , Sadek Mark
Published: July 2018

Apoptosis is an important physiological process in development and disease. Apoptotic cells (ACs) are a major source of self-antigens, but ACs usually evade immune responses. The mechanism by which ACs repress T cell adaptive immune responses is poorly understood. T cell activation is finely regulated by a balance of costimulatory signaling (mediated by the costimulatory receptor CD28 on T cells) and coinhibitory signaling (mediated by the coinhibitory ligands CD80 and PD-L1 and -2 on Antigen-Presenting Cells). Here, we found that ACs specifically upregulated the coinhibitory ligand CD80 on macrophages. Conversely, ACs did not exhibit a robust regulation of the other coinhibitory ligands on macrophages or the costimulatory receptor CD28 on T cells. We show that the robust positive regulation of CD80 by ACs requires phagocytosis of ACs by macrophages. We also demonstrate that CD80 modulation by dead cells is a specific effect of ACs, but not necrotic cells (which stimulate immune responses). These results indicate that ACs modulate the coinhibitory pathway of T cell activation via CD80, and suggest a role for CD80 in suppressing T cell responses by ACs. Understanding a mechanism of regulating adaptive immune responses to ACs, which harbor an abundance of self-antigens, may advance our understanding of mechanisms of regulating autoimmunity and facilitate future therapy development for autoimmune disorders.